Glucose biosensors and uses thereof

ABSTRACT

The present subject matter provides glucose biosensors as well as compositions, devices, and methods comprising such biosensors.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 15/776,725, filed May 16, 2018, which is a national stage application, filed under 35 U.S.C. § 371, of International Application No. PCT/US2016/050297 filed Sep. 2, 2016, which claims benefit of priority to U.S. Provisional Application No. 62/257,796, filed Nov. 20, 2015, and U.S. Provisional Application No. 62/257,784, filed Nov. 20, 2015, the entire contents of each of which are incorporated herein by reference.

INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING

The contents of the text file named “35327-516001WO_Sequence_Listing.txt”, which was created on Sep. 2, 2016 and is 587 KB in size, is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to compositions and methods for detecting and determining the concentration of glucose and/or galactose.

BACKGROUND

Biosensors are analytical tools that can be used to measure the presence of a single molecular species in a complex mixture by combining the exquisite molecular recognition properties of biological macromolecules with signal transduction mechanisms that couple ligand binding to readily detectable physical changes (Hall, Biosensors, Prentice-Hall, Englewood Cliffs, N.J.; Scheller et al., Curr. Op. Biotech. 12:35-40, 2001). Ideally, a biosensor is reagentless and, in contrast to enzyme-based assays or competitive immunoassays, does not change composition as a consequence of making the measurement (Hellinga & Marvin, Trends Biotech. 16:183-189, 1998). Most biosensors combine a naturally occurring macromolecule such as an enzyme or an antibody, with the identification of a suitable physical signal particular to the molecule in question, and the construction of a detector specific to that system (Meadows, Adv. Drug Deliv. Rev. 21:177-189, 1996). Recently, molecular engineering techniques have been explored to develop macromolecules that combine a wide range of binding specificities and affinities with a common signal transduction mechanism, to construct a generic detection system for many different analytes (Hellinga & Marvin, Trends Biotech. 16:183-189, 1998).

Escherichia coli periplasmic binding proteins are members of a protein superfamily (bacterial periplasmic binding proteins, bPBPs) (Tam & Saier, Microbiol. Rev. 57:320-346, 1993). These proteins comprise two domains linked by a hinge region (Quiocho & Ledvina, Molec. Microbiol. 20:17-25, 1996). The ligand-binding site is located at the interface between the two domains. The proteins typically adopt two conformations: a ligand-free open form, and a ligand-bound closed form, which interconvert via a hinge-bending mechanism upon ligand binding. This global, ligand-mediated conformational change has been exploited to couple ligand binding to changes in fluorescence intensity by positioning single, environmentally sensitive fluorophores in locations that undergo local conformational changes in concert with the global change (Brune et al., Biochemistry 33:8262-8271, 1994; Gilardi et al., Prot. Eng. 10:479-486, 1997; Gilardi et al., Anal. Chem. 66:3840-3847, 1994; Marvin et al., Proc. Natl. Acad. Sci. USA 94:4366-4371, 1997, Marvin and Hellinga, J. Am. Chem. Soc. 120:7-11, 1998; Tolosa et al., Anal. Biochem. 267:114-120, 1999; Dattelbaum & Lakowicz, Anal. Biochem. 291:89-95, 2001; Marvin & Hellinga, Proc. Natl. Acad. Sci. USA 98:4955-4960, 2001; Salins et al., Anal. Biochem. 294:19-26, 2001).

SUMMARY OF THE INVENTION

The invention provides improved biosensors that rapidly, reliably, and accurately detect and quantify glucose and/or galactose with significant advantages over previous systems. The present disclosure provides a biosensor for ligand, comprising a ligand-binding protein that is attached to a reporter group. The ligand may be glucose and/or galactose, and the ligand-binding protein includes a domain that binds the glucose and/or the galactose. The binding of a ligand to the ligand-binding domain of the ligand-binding protein causes a change in signaling by the reporter group. In various implementations, the biosensor may produce a signal when a ligand is bound to the ligand binding domain that is not produced (and/or that is different from a signal that is produced) when the ligand is absent from the ligand binding domain. These biosensors have widespread utility including in clinical, industrial, and environmental settings.

The glucose-binding proteins (biosensors) described herein are characterized by one conformational shape when bound to glucose and a different conformational shape when unbound to glucose, this change in shape affects the signal of a detectable label such as a fluorophore. The proteins are engineered to include a single cysteine to which the detectable label, e.g., a fluorophore is covalently attached. The biosensors are reagentless in that their monitoring mechanism requires neither additional substrates for a signal to develop, nor measurement of substrate consumption or product generation rates to determine glucose concentrations.

Among the advantages of these fluorophone-containing protein constructs is their high durability. The constructs retain their ability to bind glucose, change shape and thus detect the analyte, glucose, (a) even when immobilized (directly or indirectly)onto a solid surface such as a bead, plate, or sheet; (b) even after dessication (and subsequent reconstitution in a physiological buffer solution); (c) even when subjected to ambient conditions, e.g., conditions that can be encountered in storage and/or transportation; and (d) even when aged/stored for extended periods of time, e.g., weeks, months, or even years. Thus, the biosensors do not require refrigeration or a cold chain for distribution, permitting a wider range of applicability such as in-the-field use and reducing the cost of the sensor product.

For clinical applications, microliter volumes, e.g., 10 μl or less of a bodily fluid such as blood may be used. Moreover compared to conventional enzyme-based or antibody based assay systems, the results are achieved virtually instantaneously, e.g., within 30-60 seconds. A further advantage is that the sensors consistently and reliably bind to and detect the analyte (glucose) in complex fluids such as whole blood. Thus in a clinical setting, whole blood need not be processed, thereby reducing time and cost of the diagnostic procedure.

In non-clinical situations, e.g., industrial of commercial settings such as analysis of waste water, food or beverage production, or bioreactor/fermentation monitoring, the samples to be analyzed can be used directly upon sampling without further purification or processing, similarly reducing time and expense of the test. Moreover, the immobilized sensors need not be washed to remove unbound material following contacting the test sample with the sensors, because the unbound material (“contaminants”) do not materially affect the production of a precise, reliable detectable assay signal.

The glucose biosensors produce a dichromatic, ratiometric signal, i.e., the signal is defined as the quotient of the intensities at two independent wavelengths. The advantage of such a signal is that it provides an internally consistent reference. The self-calibrating nature of a ratiometric measurement removes the necessity for carrying out on-board calibration tests prior to each measurement.

Thus, reagentless, fluorescently responsive glucose sensors present a number of advantages over enzyme-based biosensors, including elimination of chemical transformations, elimination of substrate requirements, and self-calibration, which together lead to rapid response times, continuous monitoring capabilities, simple sample-handling, and lower cost due to simplified manufacturing and distribution processes.

Ligand-Binding Proteins

Aspects of the present subject matter provide biosensors comprising a ligand-binding protein that binds glucose and/or galactose. Ligand binding proteins that bind both glucose and galactose may be referred to herein as “glucose-galactose binding proteins” (GGBPs). Typically, a natural GGBP has a glucose dissociation constant (KD) of about 10 μM or less at room temperature. However, GGBPs may be selected, designed, or engineered to detect different (e.g., higher or lower) levels of glucose and/or galactose. The ligand-binding protein may comprise a naturally occurring protein or a protein that is modified compared to a naturally occurring protein. For example, the ligand-binding protein may comprise one or more mutations compared to a naturally occurring protein. In some embodiments, the naturally occurring protein is a naturally occurring counterpart of the ligand-binding protein (e.g., the ligand-binding protein is a mutant of the naturally occurring counterpart).

A “naturally occurring counterpart” of a mutant polypeptide is a polypeptide produced in nature from which the mutant polypeptide has been or may be derived (e.g., by one or more mutations). For example, the naturally occurring counterpart is an endogenous polypeptide produced by an organism in nature, wherein the endogenous polypeptide typically does not have one or more of the mutations present in the mutant polypeptide. For convenience and depending on context, a naturally occurring counterpart may be referred to herein for the purpose of comparison and to illustrate the location and/or presence of one or more mutations, binding activities, and/or structural features.

As used herein, a “mutation” is a difference between the amino acid sequence of a modified polypeptide/protein and a naturally occurring counterpart. A polypeptide having a mutation may be referred to as a “mutant.” Non-limiting examples of mutations include insertions, deletions, and substitutions. However, the term “mutation” excludes (i) the addition of amino acids to the N-terminus or C-terminus of a polypeptide, and (ii) the omission/deletion/replacement of a polypeptide's signal peptide (e.g., replacement with another signal peptide or with a methionine).

The addition of amino acids to the N-terminus or C-terminus of a protein via a peptide bond may be referred to herein as a “fusion” of the amino acids to the protein. Similarly, an exogenous protein fused to amino acids (e.g., another protein, a fragment, a tag, or a polypeptide moiety) at its N-terminus or C-terminus may be referred to as a “fusion protein.” The added amino acids may comprise a heterologous polypeptide, e.g., a polypeptide reporter group such as a fluorescent protein, a moiety that facilitates the isolation or modification of a polypeptide, or a moiety that facilitates the attachment of a polypeptide to a substrate or surface. As used herein, “heterologous” when referring to the added amino acids (e.g., a “polypeptide”) of a fusion protein indicates that the polypeptide is not naturally part of the protein to which it is fused in the fusion protein. For example, the sequence of a heterologous polypeptide (“added amino acids”) that is fused to a protein is encoded by an organism other than the organism from which the protein is derived, is not known to be naturally encoded by any organism, or is encoded by a gene other than the wild-type gene that encodes an endogenous version of the protein.

As used herein the term “signal peptide” refers to a short (e.g., 5-30 or 10-60 amino acids long) stretch of amino acids at the N-terminus of a protein that directs the transport of the protein. In various embodiments, the signal peptide is cleaved off during the post-translational modification of a protein by a cell. Signal peptides may also be referred to as “targeting signals,” “leader sequences,” “signal sequences,” “transit peptides,” or “localization signals.” In instances where a signal peptide is not defined for a GGBP discussed herein, the signal peptide may optionally be considered to be, e.g., the first 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N-terminus of the translated protein (compared to a protein that has not had the signal peptide removed, e.g., compared to a naturally occurring protein).

In some embodiments, the ligand-binding protein comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 1-10, 1-15, 1-20, 5-15, 5-20, 10-25, 10-50, 20-50, 25-75, 25-100 or more mutations compared to a naturally occurring protein while retaining at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%, or about 100% of the activity of the naturally occurring protein. Mutations include but are not limited to substitutions, insertions, and deletions. Non-limiting examples of ligand-binding proteins may have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 1-10, 1-15, 1-20, 5-15, 5-20, 10-25, 10-50, 20-50, 25-75, 25-100, or more substitution mutations compared to a naturally occurring protein while retaining at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%, or about 100% of the activity of the naturally occurring protein. In embodiments, at least one amino acid of the ligand-binding protein has been substituted with a cysteine. Alternatively or in addition, a ligand-binding protein may include one or more mutations that remove a cysteine, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more substitutions or deletions of a cysteine compared to a naturally occurring protein.

Alternatively, the ligand-binding protein is not a mutant. For example, a reporter group is fused to the N-terminus or the C-terminus of the ligand-binding protein.

In various embodiments, a ligand-binding protein may comprise a stretch of amino acids (e.g., the entire length of the ligand-binding protein or a portion comprising at least about 50, 100, 200, 250, 300, or 350 amino acids) in a sequence that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, or 99.5% identical to an amino acid sequence of a naturally occurring protein.

In some embodiments, the mutations are conservative, and the present subject matter includes many ligand-binding proteins in which the only mutations are substitution mutations. In non-limiting examples, a ligand-binding protein has no deletions or insertions compared to a naturally occurring protein (e.g., a naturally occurring counterpart). Alternatively, a ligand-binding protein may have (i) less than about 5, 4, 3, 2, or 1 inserted amino acids, and/or (ii) less than about 5, 4, 3, 2, or 1 deleted amino acids compared to a naturally occurring protein.

In various embodiments, a naturally occurring protein to which a ligand-binding protein is compared or has been derived (e.g., by mutation, fusion, or other modification) from a prokaryotic ligand-binding protein such as a bacterial ligand-binding protein. For example, the prokaryotic ligand-binding protein is a mutant, fragment, or variant of a natural (i.e., wild-type) bacterial protein. In various embodiments, the bacterial ligand-binding protein is from a thermophilic, mesophilic, or cryophilic prokaryotic microorganism (e.g., a thermophilic, mesophilic, or cryophilic bacterium).

A microorganism is “thermophilic” if it is capable of surviving, growing, and reproducing at temperatures between 41 and 140° C. (106 and 284° F.), inclusive. In various embodiments, a thermophilic organism has an optimal growth temperature between 41 and 140° C., or that is at least about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140° C. Many thermophiles are archaea. Thermophilic eubacteria are suggested to have been among the earliest bacteria. Thermophiles are found in various geothermally heated regions of the Earth, such as hot springs and deep sea hydrothermal vents, as well as decaying plant matter, such as peat bogs and compost. Unlike other types of microorganisms, thermophiles can survive at much hotter temperatures, whereas other bacteria would be damaged and sometimes killed if exposed to the same temperatures. Thermophiles may be classified into three groups: (1) obligate thermophiles; (2) facultative thermophiles; and (3) hyperthermophiles. Obligate thermophiles (also called extreme thermophiles) require such high temperatures for growth, whereas facultative thermophiles (also called moderate thermophiles) can thrive at high temperatures, but also at lower temperatures (e.g. below 50° C.). Hyperthermophiles are particularly extreme thermophiles for which the optimal temperatures are above 80° C. Some microorganisms can live at temperatures higher than 100° C. at large depths in the ocean where water does not boil because of high pressure. Many hyperthermophiles are also able to withstand other environmental extremes such as high acidity or radiation levels. A compound (e.g., a protein or biosensor) is “thermotolerant” if it is capable of surviving exposure to temperatures above 41° C. For example, in some embodiments a thermotolerant biosensor retains its function and does not become denatured when exposed to a temperature of about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140° C. for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30 or more minutes. In some embodiments, the thermotolerant compound survives exposure to 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140° C. under pressure.

A microorganism is “mesophilic” if it is capable of surviving, growing, and reproducing at temperatures between 20 and 40° C. (68 and 104° F.), inclusive. “Psychrophiles” or “cryophiles” are microorganisms that are capable of growth and reproduction in cold temperatures. In various embodiments, a psychrophile is capable of growth and reproduction at a temperature of 10° C. or less, e.g., between −20° C. and +10° C.

In some embodiments, the microbial protein is produced by a bacterial microorganism, an archaean microorganism, an algal microorganism, a protozoan microorganism, or a fungal microorganism. In non-limiting examples, the microbial protein is produced by a Gram-positive bacterium or a Gram-negative bacterium. In various embodiments, a biosensor comprises a modified (e.g., mutated, fused, and/or conjugated) periplasmic binding protein or a cytoplasmic binding protein.

In non-limiting examples in which the ligand-binding protein is (1) an Escherichia coli (E. coli) glucose-galactose binding protein (GGBP) (e.g., has been derived from an E. coli GGBP via mutation) or (2) has an amino acid sequence that is at least 95%, 96, 97%, 98%, or 99% identical to the amino acid sequence of E. coli GGBP, the ligand-binding protein comprises a mutation other than a mutation of amino acid Y10, D14, N15, F16, N91, K92, E93, S112, S115, E149, H152, D154, A155, R158, M182, W183, N211, D236, L255, N256, D257, P294, or V296, wherein each amino acid position is numbered as in (SEQ ID NO: 17).

In certain embodiments, the ligand-binding protein is not derived from (e.g., by mutation, fusion, or other modification) an E. coli protein (such as ecGGBP) and does not comprise an amino acid sequence that is identical to the amino acid sequence of ecGGBP. For example, the naturally occurring counterpart of the ligand-binding protein is not an E. coli GGBP (e.g., the ligand-binding protein is not a mutant of, fusion protein comprising, or other variant of an E. coli GGBP). In some embodiments, the amino acid sequence of the ligand-binding protein is less than about 100%, 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 59%, 58%, 57%, 56%, 55%, 54%, 53%, 52%, 51%, 50%, 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, or 15% identical to an E. coli GGBP protein having amino acids in the sequence set forth as SEQ ID NO: 1, 16, or 17.

Aspects of the present subject matter provide a ligand-binding protein with a mutation that alters the interaction of the ligand-binding protein with a ligand (e.g., glucose and/or galactose). For example, the ligand-binding protein comprises a mutation that alters the interaction of the ligand-binding protein with the ligand compared to a naturally occurring counterpart. In some embodiments, the ligand-binding protein comprises a mutation that alters the interaction of an amino acid of the ligand-binding protein with a water molecule compared to a naturally occurring counterpart.

In some embodiments, the ligand-binding protein does not comprise a signal peptide. For example, the signal peptide (e.g., that is present in a naturally occurring counterpart) may be replaced with a methionine.

Exemplary implementations relate to a ligand such as glucose or galactose, wherein the ligand-binding protein comprises a GGBP. For example, the GGBP may comprise a mutant of, a fragment of, or a fusion protein comprising a microbial GGBP. In embodiments, the GGBP is not a mutant or fragment to which a heterologous polypeptide has been attached or added. In some embodiments, the ligand-binding protein has an affinity (KD) for glucose and/or galactose within the concentration range of glucose and/or galactose in a subject. In certain embodiments, the ligand-binding protein has an affinity (KD) for glucose in the range of about 0.2 mM to about 100 mM, about 0.1 mmol/L to about 120 mmol/L, or about 4 mmol/L to about 33 mmol/L. In various embodiments, the ligand-binding protein has an affinity (KD) for galactose in the range of about 0.8 mM to about 100 mM or about 0.2 mM to about 400 mM. The biosensor is capable of detecting glucose in, e.g. the hypoglycemic, euglycemic, hyperglycemic, or hyperglycemic-hyperosmotic range. Thus, unlike previous glucose sensors, the ratiometric reagentless glucose biosensors produce precise measurements over an extended glucose concentration range from hypoglycemic, euglycemic, hyperglycemic, as well as the hyperglycemic-hyperosmotic range in sample volumes of less than 10 μl. In some embodiments, the ligand-binding protein comprises a mutation that alters (e.g., increases or decreases) the interaction of the mutant with bound glucose compared to a naturally occurring protein (e.g., a microbial GGBP), wherein the interaction is with a portion of the glucose selected from the group consisting of 1-hydroxyl, 2-hydroxyl, 3-hydroxyl, 4-hydoxyl, 6-hydroxyl, pyranose ring, or any combination thereof. In non-limiting examples, the ligand-binding protein comprises a mutation that alters (e.g., increases or decreases) the mutant's affinity and/or specificity for glucose and/or galactose compared to a the unmutated ligand-binding protein (e.g., a microbial GGBP). In certain embodiments, the ligand-binding protein comprises a mutation that alters the interaction between the protein and bound glucose and/or galactose, a mutation that alters the equilibrium between the open and closed states of the ligand-binding protein, a mutation that alters the interaction between the ligand-binding protein and a reporter group (such as a fluorescent conjugate, e.g., the interaction with a carbonyl group or a naphthalene ring of a prodan-derived fluorophore such as Acrylodan or Badan), and/or a mutation that impacts indirect interactions that alter the geometry of the ligand binding site. In various embodiments, the mutation does not reduce, or negligibly impacts, the thermostability of the ligand-binding protein. In some embodiments, the mutation alters the thermostability of the ligand-binding protein by less than about 1, 2, 3, 4, 5, or 10° C.

The present subject matter provides a GGBP that is or is a mutant of: an Escherichia sp. (e.g., E. albertii, E. coli, E. fergusonii, E. hermannii, or E. vulneris) GGBP; a Thermoanaerobacter sp. (e.g., T. acetoethylicus, T. brockii, T. ethanolicus, T. italicus, T. kivui, T. mathranii, T. pseudethanolicus, T. siderophilus, T. sulfurigignens, T. sulfurophilus, T. thermocopriae, T. thermohydrosulfuricus, T. thermosaccharolyticum, T. uzonensis, or T. wiegelii) GGBP; a Clostridium sp. (e.g., C. absonum, C. aceticum, C. acetireducens, C. acetobutylicum, C. acidisoli, C. aciditolerans, C. acidurici, C. aerotolerans, C. aestuarii, C. akagii, C. aldenense, C. aldrichii, C. algidicarni, C. algidixylanolyticum, C. algifaecis, C. algoriphilum, C. alkalicellulosi, C. aminophilum, C. aminovalericum, C. amygdalinum, C. amylolyticum, C. arbusti, C. arcticum, C. argentinense, C. asparagiforme, C. aurantibutyricum, C. autoethanogenum, C. baratii, C. barkeri, C. bartlettii, C. beijerinckii, C. bifermentans, C. bolteae, C. bornimense, C. botulinum, C. bowmanii, C. bryantii, C. butyricum, C. cadaveris, C. caenicola, C. caminithermale, C. carboxidivorans, C. carnis, C. cavendishii, C. celatum, C. celerecrescens, C. cellobioparum, C. cellulofermentans, C. cellulolyticum, C. cellulosi, C. cellulovorans, C. chartatabidum, C. chauvoei, C. chromiireducens, C. citroniae, C. clariflavum, C. clostridioforme, C. coccoides, C. cochlearium, C. colletant, C. colicanis, C. colinum, C. collagenovorans, C. cylindrosporum, C. difficile, C. diolis, C. disporicum, C. drakei, C. durum, C. estertheticum, C. estertheticum estertheticum, C. estertheticum laramiense, C. fallax, C. felsineum, C. fervidum, C. fimetarium, C. formicaceticum, C. frigidicarnis, C. frigoris, C. ganghwense, C. gasigenes, C. ghonii, C. glycolicum, C. glycyrrhizinilyticum, C. grantii, C. haemolyticum, C. halophilum, C. hastiforme, C. hathewayi, C. herbivorans, C. hiranonis, C. histolyticum, C. homopropionicum, C. huakuii, C. hungatei, C. hydrogeniformans, C. hydroxybenzoicum, C. hylemonae, C. jejuense, C. indolis, C. innocuum, C. intestinale, C. irregulare, C. isatidis, C. josui, C. kluyveri, C. lactatifermentans, C. lacusfryxellense, C. laramiense, C. lavalense, C. lentocellum, C. lentoputrescens, C. leptum, C. limosum, C. litorale, C. lituseburense, C. ljungdahlii, C. lortetii, C. lundense, C. magnum, C. malenominatum, C. mangenotii, C. mayombei, C. methoxybenzovorans, C. methylpentosum, C. neopropionicum, C. nexile, C. nitrophenolicum, C. novyi, C. oceanicum, C. orbiscindens, C. oroticum, C. oxalicum, C. papyrosolvens, C. paradoxum, C. paraperfringens, C. paraputrificum, C. pascui, C. pasteurianum, C. peptidivorans, C. perenne, C. perfringens, C. pfennigii, C. phytofermentans, C. piliforme, C. polysaccharolyticum, C. populeti, C. propionicum, C. proteoclasticum, C. proteolyticum, C. psychrophilum, C. puniceum, C. purinilyticum, C. putrefaciens, C. putrificum, C. quercicolum, C. quinii, C. ramosum, C. rectum, C. roseum, C. saccharobutylicum, C. saccharogumia, C. saccharolyticum, C. saccharoperbutylacetonicum, C. sardiniense, C. sartagoforme, C. scatologenes, C. schirmacherense, C. scindens, C. septicum, C. sordellii, C. sphenoides, C. spiroforme, C. sporogenes, C. sporosphaeroides, C. stercorarium, C. stercorarium leptospartum, C. stercorarium stercorarium, C. stercorarium thermolacticum, C. sticklandii, C. straminisolvens, C. subterminale, C. sufflavum, C. sulfidigenes, C. symbiosum, C. tagluense, C. tepidiprofundi, C. termitidis, C. tertium, C. tetani, Clostridium tetanomorphum, C. thermaceticum, C. thermautotrophicum, C. thermoalcaliphilum, C. thermobutyricum, C. thermocellum, C. thermocopriae, C. thermohydrosulfuricum, C. thermolacticum, C. thermopalmarium, C. thermopapyrolyticum, C. thermosaccharolyticum, C. thermosuccinogenes, C. thermosulfurigenes, C. thiosulfatireducens, C. tyrobutyricum, C. uliginosum, C. ultunense, C. villosum, C. vincentii, C. viride, C. xylanolyticum, or C. xylanovorans) GGBP; a Salmonella sp. [e.g., S. bongori, S. enterica, S. enterica subspecies enterica, S. enterica subspecies salamae, S. enterica subspecies arizonae, S. enterica subspecies diarizonae, S. enterica subspecies houtenae, S. enterica subspecies indica, or S. enterica subspecies enterica serovar Typhimurium (S. typhimurium)] GGBP; a Caldicellulosiruptor sp. (e.g., C. saccharolyticus, C. acetigenus, C. bescii, C. changbaiensis, C. hydrothermalis, Caldicellulosiruptor hydrother, C. kristjanssonii, C. kronotskyensis, C. lactoaceticus, C. owensensis, or C. obsidiansis) GGBP; a Paenibacillus sp. (e.g., P. agarexedens, P. agaridevorans, P. alginolyticus, P. alkaliterrae, P. alvei, P. amylolyticus, P. anaericanus, P. antarcticus, P. assamensis, P. azoreducens, P. azotofixans, P. barcinonensis, P. borealis, P. brasilensis, P. brassicae, P. campinasensis, P. chinjuensis, P. chitinolyticus, P. chondroitinus, P. cineris, P. cookii, P. curdlanolyticus, P. daejeonensis, P. dendritiformis, P. durum, P. ehimensis, P. elgii, P. favisporus, P. glucanolyticus, P. glycanilyticus, P. gordonae, P. graminis, P. granivorans, P. hodogayensis, P. illinoisensis, P. jamilae, P. kobensis, P. koleovorans, P. koreensis, P. kribbensis, P. lactis, P. larvae, P. lautus, P. lentimorbus, P. macerans, P. macquariensis, P. massiliensis, P. mendelii, P. motobuensis, P. naphthalenovorans, P. nematophilus, P. odorifer, P. pabuli, P. peoriae, P. phoenicis, P. phyllosphaerae, P. polymyxa, P. popilliae, P. pulvifaciens, P. rhizosphaerae, P. sanguinis, P. stellifer, P. terrae, P. thiaminolyticus, P. timonensis, P. tylopili, P. turicensis, P. validus, P. vortex, P. vulneris, P. wynnii, P. xylanilyticus) GGBP; a Butyrivibrio sp. (e.g., B. proteoclasticus, B. crossotus, B. fibrisolvens, or B. hungatei) GGBP; a Roseburia sp. (e.g., R. intestinalis, R. faecis, R. hominis, or R. inulinivorans) GGBP; a Faecalibacterium sp. (e.g., F. prausnitzii) GGBP; an Erysipelothrix sp. (e.g., E. rhusiopathiae, E. inopinata, or E. tonsillarum) GGBP; or an Eubacterium sp. (e.g., E. rectale, E. acidaminophilum, E. nodatum, E. oxidoreducens, or E. foedans) GGBP.

In various embodiments, a biosensor comprises a GGBP that is or is a mutant of: an Escherichia coli GGBP (ecGGBP; SEQ ID NO: 1), a Thermoanaerobacter thermosaccharolyticum GGBP (ttGGBP; SEQ ID NO: 2), a Salmonella typhimurium GGBP (stGGBP; SEQ ID NO: 3), a Caldicellulosiruptor hydrothermalis GGBP (chyGGBP; SEQ ID NO: 4), a Caldicellulosiruptor obsidiansis GGBP (cobGGBP; SEQ ID NO: 5), a Paenibacillus sp. GGBP (pspGGBP; SEQ ID NO: 6); a Clostridium saccharolyticum GGBP (csaGGBP; SEQ ID NO: 7); a Clostridium autoethanogenum GGBP (cauGGBP; SEQ ID NO: 12); a Clostridium ljungdahlii GGBP (cljGGBP; SEQ ID NO: 11); a Butyrivibrio proteoclasticus GGBP (bprGGBP; SEQ ID NO: 8); a Roseburia intestinalis GGBP (rinGGBP_A; SEQ ID NO: 9 or rinGGBP_B; SEQ ID NO: 13); a Faecalibacterium prausnitzii GGBP (fprGGBP; SEQ ID NO: 10); a Erysipelothrix rhusiopathiae GGBP (erhGGBP; SEQ ID NO: 14); or a Eubacterium rectale GGBP (ereGGBP; SEQ ID NO: 15). In some embodiments, the GGBP comprises an amino acid sequence that is between 75% and 10% identical (e.g., between 25% and 50% identical) to the amino acid sequence of ecGGBP (SEQ ID NO: 1 or 17), ttGGBP (SEQ ID NO: 2 or 18), stGGBP (SEQ ID NO: 3 or 19), chyGGBP (SEQ ID NO: 4 or 20), pspGGBP (SEQ ID NO: 6 or 22); csaGGBP (SEQ ID NO: 7 or 23); bprGGBP (SEQ ID NO: 8 or 24); rinGGBP_A (SEQ ID NO: 9 or 25); rinGGBP_B (SEQ ID NO: 13 or 29); fprGGBP (SEQ ID NO: 10 or 26); cljGGBP (SEQ ID NO: 11 or 27); cauGGBP (SEQ ID NO: 12 or 28); erhGGBP (SEQ ID NO: 14 or 30); and/or ereGGBP (SEQ ID NO: 15 or 31).

Aspects of the present subject matter include a GGBP that is or is a mutant of a protein listed in Table 1, e.g., the protein numbered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138 in Table 1.

With regard to a defined polypeptide, % identity figures higher or lower than those provided herein will encompass various embodiments. Thus, where applicable, in light of a minimum % identity figure, a polypeptide may comprises an amino acid sequence which is at least 60%, 65%, 70%, 75%, 76%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. Where applicable, in light of a maximum % identity to a reference sequence, a polypeptide may comprise an amino acid sequence which is less than 75%, 70%, 65%, 60%, 59%, 58%, 57%, 56%, 55%, 54%, 53%, 52%, 51%, 50%, 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, or 15% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. In certain embodiments, a polypeptide comprises amino acids in a sequence that is preferably at least about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% and less than about 75%, 70%, 65%, 60%, 55%, 50%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, or 30% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. Non-limiting examples of reference proteins and amino acid sequences disclosed herein include:

-   -   (i) a glucose-galactose binding protein from Escherichia coli         (ecGGBP; genome, NC_002695; protein, WP_032329053, SEQ ID NO:         1);     -   (ii) a glucose-galactose binding protein from         Thermoanaerobacterium thermosaccharolyticum (ttGGBP; genome,         NC_014410; protein, YP_003852930.1, SEQ ID NO: 2);     -   (iii) a glucose-galactose binding protein from Salmonella         typhimurium (stGGBP; genome, NC_003197; protein, WP_001036943,         SEQ ID NO: 3);     -   (iv) a glucose-galactose binding protein from         Caldicellulosiruptor hydrothermalis (chyGGBP; genome, NC_014652;         protein identifier, YP_003991244.1, SEQ ID NO: 4);     -   (v) a glucose-galactose binding protein from         Caldicellulosiruptor obsidiansis (cobGGBP; genome, NC_014392;         protein, YP_003839461.1, SEQ ID NO: 5);     -   (vi) a glucose-galactose binding protein from Paenibacillus sp.         (pspGGBP; genome, NC_013406; protein, YP_003243743.1, SEQ ID NO:         6);     -   (vii) a glucose-galactose binding protein from Clostridium         saccharolyticum (csaGGBP; genome, NC_014376; protein,         YP_003822565.1, SEQ ID NO: 7);     -   (viii) a glucose-galactose binding protein from Butyrivibrio         proteoclasticus (bprGGBP; genome, NC_014387; protein,         YP_003830205.1, SEQ ID NO: 8);     -   (ix) a glucose-galactose binding protein from Roseburia         intestinalis (rinGGBP_A; genome, NC_021012; protein,         YP_007778116.1, SEQ ID NO: 9);     -   (x) a glucose-galactose binding protein from Faecalibacterium         prausnitzii (fprGGBP; genome, NC_021020; protein,         YP_007799070.1, SEQ ID NO: 10);     -   (xi) a glucose-galactose binding protein from Clostridium         ljungdahlii (cljGGBP; genome, NC_014328; protein, CLJU_c08950,         SEQ ID NO: 11);     -   (xii) a glucose-galactose binding protein from Clostridium         autoethanogenum (cauGGBP; genome, NC_022592; protein,         CAETHG_2989, SEQ ID NO: 12);     -   (xiii) a glucose-galactose binding protein from Roseburia         intestinalis (rinGGBP_B; genome, NC_021012; protein,         YP_007778124.1, SEQ ID NO: 13);     -   (xiv) a glucose-galactose binding protein from Erysipelothrix         rhusiopathiae (erhGGBP; genome, NC_015601; protein,         YP_004561181.1, SEQ ID NO: 14); and     -   (xv) a glucose-galactose binding protein from Eubacterium         rectale (ereGGBP; genome, NC_012781; protein, YP_002936409.1,         SEQ ID NO: 15).

The GGBPs disclosed herein may optionally be fused (e.g., at their N-terminal and/or C-terminal ends) to a motif comprising a stretch of amino acids that facilitates the isolation or other manipulation such as conjugation to a moiety or immobilization on a substrate such as a plastic, a cellulose product such as paper, polymer, metal, noble metal, semi-conductor, or quantum dot (e.g., a fluorescent quantum dot). A non-limiting example of such a stretch of amino acids has the sequence: GGSHHHHHH (SEQ ID NO: 104). This motif is not required for and is not believed to influence or affect ligand-binding activity or signal transduction. For example, each of SEQ ID NOs: 32-103 (and the non-limiting examples of otherproteins used in the experiments disclosed herein) comprises this motif (SEQ ID NO: 104). Alternatively or in addition, a ligand-binding protein may be fused to a heterologous polypeptide or “added amino acids” that facilitates the attachment therof to a surface, such as the surface of a device.

In some embodiments, a polypeptide comprises 1, 2, 3, 4, 5, or more substitutions or deletions of a cysteine compared to the naturally occurring counterpart of the polypeptide (i.e., 1, 2, 3, 4, 5, or more native cysteines have been removed), e.g., 1, 2, 3, 4, 5, or more cysteine to alanine substitutions compared to the naturally occurring counterpart of the polypeptide. In some embodiments, all of cysteines of a polypeptide have been deleted and/or substituted compared to its natural counterpart.

In embodiments, the amino acid sequence of a protein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 mutations compared to its naturally occurring counterpart. In some embodiments, less than 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 of the mutations is a deletion or insertion of 1, 2, 3, 4, or 5 or no more than 1, 2, 3, 4, or 5 amino acids. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or more of the mutations is a substitution mutation. In certain embodiments, every mutation to a protein compared to its naturally occurring counterpart is a substitution mutation. In various embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more or all of the mutations to a protein compared to its naturally occurring counterpart is a conservative substitution mutation.

In various embodiments, a polypeptide does not have any insertion or deletion compared to its natural counterpart, other than (optionally) the removal of the signal peptide and/or the fusion of compounds such as another polypeptide at the N-terminus or C-terminus thereof.

Ligand-Binding Proteins Comprising a Primary Complementary Surface (PCS)

The following BLAST parameters are used to identify sequence homologues of GGBP: (1) Expect threshold is 10.0; (2) Gap cost is Existence:11 and Extension:1; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is “on.” Such an alignment may be generated using the ProteinHunter program. The ProteinHunter package always executes BLAST searches, with the following command

“blastall -p blastp -m 8 -b 50000 -d %s -i <INPUT FILE> -o <OUTPUT FILE>”

where <INPUT FILE> and <OUTPUT FILE> specify the input and output files, respectively for a given calculation. This command executes the BLAST alignment program for protein sequences with default parameters, intrinsically set by the program. The BLAST program version is 2.2.24.

Sequence homologues of GGBP identified using BLAST may be aligned with ecGGBP using ClustalW to identify homologues that share a PCS with ecGGBP as discussed below.

Aspects of the present subject matter provide ligand-binding proteins that share a PCS with a GGBP disclosed herein. In embodiments, the PCS comprises at least about 5, 6, 7, 8, 9, or 10 amino acid positions used to identify a glucose-galactose binding protein. For example, the PCS of ecGGBP may comprise positions 14, 16, 91, 152, 154, 158, 183, 211, 236, and 256, wherein each position is counted as in SEQ ID NO: 17. In various embodiments, a protein shares a PCS with ecGGBP if the amino acid sequence of the protein has

(i) D or N at the position that aligns with position 14 of ecGGBP;

(ii) F, Y, or W at the position that aligns with position 16 of ecGGBP;

(iii) N or D at the position that aligns with position 91 of ecGGBP;

(iv) H, N, or Q at the position that aligns with position 152 of ecGGBP;

(v) D or N at the position that aligns with position 154 of ecGGBP;

(vi) R at the position that aligns with position 158 of ecGGBP;

(vii) W, F, or Y at the position that aligns with position 183 of ecGGBP;

(viii) N or D at the position that aligns with position 211 of ecGGBP;

(ix) D or N at the position that aligns with position 236 of ecGGBP; and

(x) N or D at the position that aligns with position 256 of ecGGBP,

wherein the alignment between ecGGBP (SEQ ID NO: 17) and the protein is constructed using the ClustalW alignment program.

The ProteinHunter package always executes multiple sequence alignments with the following command

“clustalw -infile=<INPUT FILE> -outfile=<OUTPUTFILE> -align -quiet”

This command executes the CLUSTALW multi-sequence alignment program for protein sequences. There are no user-specified parameter settings that alter the alignment behavior of the program. The CLUSTALW program version is 2.1.

For convenience and depending on context, a position that aligns with a stated position of ecGGBP may be referred to herein as “equivalent” to the stated position.

Exemplary Ligand-Binding Proteins

Various biosensors provided herein comprise glucose-galactose binding proteins, such as glucose-galactose binding proteins that have altered amino acid sequences compared to their naturally occurring counterparts. In embodiments, such proteins are conjugated to reporter groups. ecGGBP is a non-limiting reference protein respect to glucose-galactose binding proteins. An alignment of ecGGBP with other polypeptides is provided in FIG. 3.

In various embodiments, a polypeptide of the present disclosure comprises

-   -   (a) an amino acid that is preferably (i) at least about 10%,         11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%,         24%, 25%, 26%, 27%, 28%, 29%, or 30%, and (ii) less than about         75%, 70%, 65%, 60%, 55%, 50%, 45%, 44%, 43%, 42%, 41%, 40%, 39%,         38%, 37%, 36%, or 35% identical to ecGGBP;     -   (b) a cysteine substitution (compared to its naturally occurring         counterpart) within a stretch of at least 5, 10, or 20 amino         acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%,         90%, or 95% identity to a stretch of consecutive amino acids         including position 183 of ecGGBP (e.g., a tryptophan to cysteine         substitution);     -   (c) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 14 of ecGGBP;     -   (d) a stretch of amino acids in the sequence         -   a. IYKX₁DDX₂FM (where X₁ is any amino acid, or where X₁ is             Y, F, Q, or K; and where X₂ is any amino acid, or where X₂             is N or T) (SEQ ID NO: 182),         -   b. YKX₁DDX₂FM (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 183),         -   c. YKX₁DDX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 184),         -   d. KX₁DDX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 185),         -   e. YKXDD (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 186),         -   f. KXDD (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 187),         -   g. DDXF (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 188),         -   h. DX₁FMX₂X₃VR (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 189),         -   i. DX₁FMX₂X₃V (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 190),         -   j. DXFM (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 191),         -   k. IYKX₁DNX₂FM (where X₁ is any amino acid, or where X₁ is             Y, F, Q, or K; and where X₂ is any amino acid, or where X₂             is N or T) (SEQ ID NO: 192),         -   l. YKX₁DNX₂FM (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 193),         -   m. YKX₁DNX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 194),         -   n. KX₁DNX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 195),         -   o. YKXDN (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 196),         -   p. KXDN (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 197),         -   q. DNXF (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 198),         -   r. NX₁FMX₂X₃VR (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 199),         -   s. NX₁FMX₂X₃V (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 200),         -   t. NXFM (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 201);     -   (e) a stretch of amino acids in the sequence         -   a. IYKX₁DDX₂FM (where X₁ is any amino acid, or where X₁ is             Y, F, Q, or K; and where X₂ is any amino acid, or where X₂             is N or T) (SEQ ID NO: 182),         -   b. YKX₁DDX₂FM (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 183),         -   c. YKX₁DDX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 184),         -   d. KX₁DDX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 185),         -   e. YKXDD (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 186),         -   f. KXDD (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 187),         -   g. DDXF (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 188),         -   h. DX₁FMX₂X₃VR (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 189),         -   i. DX₁FMX₂X₃V (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 190),         -   j. DXFM (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 191),         -   k. IYKX₁DNX₂FM (where X₁ is any amino acid, or where X₁ is             Y, F, Q, or K; and where X₂ is any amino acid, or where X₂             is N or T) (SEQ ID NO: 192),         -   l. YKX₁DNX₂FM (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 193),         -   m. YKX₁DNX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 194),         -   n. KX₁DNX₂F (where X₁ is any amino acid, or where X₁ is Y,             F, Q, or K; and where X₂ is any amino acid, or where X₂ is N             or T) (SEQ ID NO: 195),         -   o. YKXDN (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 196),         -   p. KXDN (where X is any amino acid, or where X is Y, F, Q,             or K) (SEQ ID NO: 197),         -   q. DNXF (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 198),         -   r. NX₁FMX₂X₃VR (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 199),         -   s. NX₁FMX₂X₃V (where X₁ is any amino acid, or where X₁ is N             or T; where X₂ is any amino acid, or where X₂ is S, T, G;             and where X₃ is any amino acid, or where X₃ is V, G, E,             or L) (SEQ ID NO: 200), or         -   t. NXFM (where X is any amino acid, or where X is N or T)             (SEQ ID NO: 201),     -   within about 50, 45, 40, 35, 20, or 15 amino acids of the         N-terminus of the polypeptide, including or not including the         amino acids of the signal peptide (also referred to herein as         the leader peptide) of its natural counterpart;     -   (f) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 91 of ecGGBP     -   (g) a stretch of amino acids having the sequence

(SEQ ID NO: 202) a. PVVFFNKEP, 

-   -   -   b. PVVFXNKEP (where X is any amino acid, or where X is F, L,             V, or I) (SEQ ID NO: 203),         -   c. PVVFFNXEP (where X is any amino acid, or where X is K, R,             E, or G) (SEQ ID NO: 204),         -   d. PVVFX₁NX₂EP (where X₁ is any amino acid, or where X₁ is             F, L, V, or I; and where X₂ is any amino acid, or where X₂             is K, R, E, or G) (SEQ ID NO: 205),         -   e. VVFX₁NX₂EP (where X₁ is any amino acid, or where X₁ is F,             L, V, or I; and where X₂ is any amino acid, or where X₂ is             K, R, E, or G) (SEQ ID NO: 206),         -   f. VFX₁NX₂EP (where X₁ is any amino acid, or where X₁ is F,             L, V, or I; and where X₂ is any amino acid, or where X₂ is             K, R, E, or G) (SEQ ID NO: 207),         -   g. PVVFX₁NX₂E (where X₁ is any amino acid, or where X₁ is F,             L, V, or I; and where X₂ is any amino acid, or where X₂ is             K, R, E, or G) (SEQ ID NO: 208),         -   h. PVVFXN (where X is any amino acid, or where X is F, L, V,             or I) (SEQ ID NO: 209),         -   i. PX₁VFX₂N (where X₁ is any amino acid, or where X₁ is V,             I, L, or T; and where X₂ is any amino acid, or where X₂ is             F, L, V, or I) (SEQ ID NO: 210),         -   j. PVX₁FX₂N (where X₁ is any amino acid, or where X₁ is V,             I, L, or T; and where X₂ is any amino acid, or where X₂ is             F, L, V, or I) (SEQ ID NO: 211),         -   k. FX₁NX₂EP (where X₁ is any amino acid, or where X₁ is F,             L, V, or I; and where X₂ is any amino acid, or where X₂ is             K, R, E, or G) (SEQ ID NO: 212), or         -   l. FX₁NX₂E (where X₁ is any amino acid, or where X₁ is F, L,             V, or I; and where X₂ is any amino acid, or where X₂ is K,             R, E, or G) (SEQ ID NO: 213);

    -   (h) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 150, 155, or 160 of         ecGGBP;

    -   (i) a stretch of amino acids having the sequence

(SEQ ID NO: 214) a. PGHPDAEART,

-   -   -   b. PGHX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 215),         -   c. GHX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 216),         -   d. HX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 217),         -   e. DAX₁X₂RT (where X₁ is any amino acid, or where X₁ is E,             I, K, or Q;

and where X₂ is any amino acid, or where X₂ is A, L, V, K, Q, or Y) (SEQ ID NO: 218),

-   -   -   f. PGHX₁DAX₂X₃R (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 219),         -   g. PGHXDA (where X is any amino acid, or where X is P, Q, V,             I, or E) (SEQ ID NO: 220),         -   h. PGHXD (where X is any amino acid, or where X is P, Q, V,             I, or E) (SEQ ID NO: 221),         -   i. PGNPDAEART (SEQ ID NO: 222),         -   j. PGNX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 223),         -   k. GNX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 224),         -   l. NX₁DAX₂X₃RT (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 225),         -   m. PGNX₁DAX₂X₃R (where X₁ is any amino acid, or where X₁ is             P, Q, V, I, or E; where X₂ is any amino acid, or where X₂ is             E, I, K, or Q; and where X₃ is any amino acid, or where X₃             is A, L, V, K, Q, or Y) (SEQ ID NO: 226),         -   n. PGNXDA (where X is any amino acid, or where X is P, Q, V,             I, or E) (SEQ ID NO: 227), or         -   o. PGNXD (where X is any amino acid, or where X is P, Q, V,             I, or E) (SEQ ID NO: 228);

    -   (j) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 183 of ecGGBP;

    -   (k) a stretch of amino acids having the sequence

(SEQ ID NO: 229) a. DTAMWD, (SEQ ID NO: 230) b. DTAMCD, (SEQ ID NO: 231) c. DTAMW, (SEQ ID NO: 232) d. DTAMC, (SEQ ID NO: 233) e. TAMWD, (SEQ ID NO: 234) f. TAMCD,

-   -   -   g. AX₁WX₂X₃ (where X₁ is any amino acid, or where X₁ is M or             N; where X₂ is any amino acid, or where X₂ is D or N; and             where X₃ is any amino acid, or where X₃ is T or R) (SEQ ID             NO: 235), or         -   h. AX₁CX₂X₃ (where X₁ is any amino acid, or where X₁ is M or             N; where X₂ is any amino acid, or where X₂ is D or N; and             where X₃ is any amino acid, or where X₃ is T or R) (SEQ ID             NO: 236);

    -   (l) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 210 of ecGGBP;

    -   (m) a stretch of amino acids having the sequence

(SEQ ID NO: 237) a. IEVVIANND, (SEQ ID NO: 238) b. EVVIANND, (SEQ ID NO: 239) c. IEVVIANN, (SEQ ID NO: 240) d. EVVIANN,

-   -   -   e. IEX₁VX₂X₃NND (where X₁ is any amino acid, or where X₁ is             V, A, L, or C; where X₂ is any amino acid, or where X₂ is I,             F, or L; and where X₃ is any amino acid, or where X₃ is A             or C) (SEQ ID NO: 241),         -   f. IEX₁VX₂X₃NN (where X₁ is any amino acid, or where X₁ is             V, A, L, or C; where X₂ is any amino acid, or where X₂ is I,             F, or L; and where X₃ is any amino acid, or where X₃ is A             or C) (SEQ ID NO: 242),         -   g. EX₁VX₂X₃NND (where X₁ is any amino acid, or where X₁ is             V, A, L, or C; where X₂ is any amino acid, or where X₂ is I,             F, or L; and where X₃ is any amino acid, or where X₃ is A             or C) (SEQ ID NO: 243), or         -   h. EXiVX₂X₃NN (where X₁ is any amino acid, or where X₁ is V,             A, L, or C; where X₂ is any amino acid, or where X₂ is I, F,             or L; and where X₃ is any amino acid, or where X₃ is A or C)             (SEQ ID NO: 244);

    -   (n) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 235 or 240 of ecGGBP;

    -   (o) a stretch of amino acids having the sequence

(SEQ ID NO: 245) a. PVFGVDA, (SEQ ID NO: 246) b. VFGVDA, (SEQ ID NO: 247) c. PVFGVD, (SEQ ID NO: 248) d. FGVDA, (SEQ ID NO: 249) e. PVXGVDA, (where X is any amino acid or where X is F, V, or I) 

-   -   -   f. VXGVDA (where X is any amino acid or where X is F, V,             or I) (SEQ ID NO: 250),         -   g. PVXGVD (where X is any amino acid or where X is F, V,             or I) (SEQ ID NO: 251), or         -   h. VXGVD (where X is any amino acid or where X is F, V,             or I) (SEQ ID NO: 252);

    -   (p) a stretch of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,         15, 20, 25, or 30 amino acids having at least about 50%, 55%,         60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of         consecutive amino acids including position 255 or 260 of ecGGBP

    -   (q) a stretch of amino acids having the sequence GTVLNDA (SEQ ID         NO: 253), GTVLND (SEQ ID NO: 254), GTVLN (SEQ ID NO: 255), or         TVLND (SEQ ID NO: 256);

    -   (r) no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 15 deleted or         inserted amino acids compared to ecGGBP, not including added         amino acids added to the N-terminus or C-terminus of the         polypeptide compared to its natural counterpart, and including         or not including the signal peptide of the natural counterpart         of the polypeptide;

    -   (s) at least 8, 9, 10, or 11, or exactly 8, 9, 10, or 11         α-helices; and/or

    -   (t) at least 9, 10, 11, or 12 β-sheets or exactly 9, 10, 11, or         12 β-sheets.

In embodiments, two or more or each of features (c)-(q) above occurs in the polypeptide in the order listed above as the amino acid sequence of the polypeptide is viewed or read from the N-terminus to the C-terminus (with additional features and/or amino acid sequences therebetween). For example, the polypeptide may have an N-terminus, followed by feature (c), (d), or (e), followed by feature (f) or (g), followed by feature (h) or (i), followed by feature (j) or (k), followed by feature (l) or (m), followed by feature (n) or (o), followed by feature (p) or (q), followed by the C-terminus.

As used herein when referring to the order of features in an amino acid read from the N terminus to the C-terminus, a first feature is “followed by” a second feature when the second feature occurs after the first feature in the amino acid sequence. The words “followed by” do not require that the second feature immediately follow or be close to the first feature. For example, the N-terminus is followed by the C-terminus.

The features listed above are not limiting and may be combined with any other relevant features disclosed herein, including those listed below.

In some embodiments the polypeptide has the following sequence:

ZZZZ!GVXIY K%DDXFMXXV RXAXXXXXXX XXXX#XXZZD  XQNXQXXQN# X!DXXXXKXX XX$X1NXVDX XAAGXXI#KA  XXXNXPVVFX NXEPXXXX$X XXDKXYYVGX XXX#SGXXXG  #XXXXXWXXX XXXDXNX#GX x#%V$xxG#P GHXDAxxRTX %X!XXXXXXG IXXXXLXXDX AXWDXXXXXX KMXXXLXXZX X#XIEXVXXN NDXMA$GA!E ALKXZZZZXX XXXXPVXGVD  AXXXXXXXXX XGX$XGTVLN DAXXQXKAXX XXAXXLXXGZ XXXX#XXXXX IZ#XKX!X!X YXX!XKDNXX #ZZZZZZZZ wherein each

Z is, individually, any amino acid or is absent,

X is, individually, any amino acid,

! is, individually, I or V,

S is, individually, L or M,

% is, individually, F or Y, and

# is, individually, N, D, Q, or E.

In a non-limiting example, the glucose-galactose binding polypeptide comprises an N-terminal domain and a C-terminal domain connected by a flexible hinge, with the ligand-binding site (the ligand binding domain) located in the cleft between the N-terminal and the C-terminal domain.

In some embodiments, the glucose-galactose binding polypeptide comprises, from the N-terminus to the C-terminus, a first β-sheet (β1), followed by a first α-helix (α1), followed by a second β-sheet (β2), followed by a second α-helix (α2), followed by a third β-sheet (β3), followed by a third α-helix (α3), followed by a fourth β-sheet (β4), followed by a fourth α-helix (α4), followed by a fifth β-sheet (β5), followed by a first inter-domain hinge segment (h1), followed by a fifth α-helix (α5), followed by a sixth β-sheet (β6), followed by a sixth α-helix (α6), followed by a seventh β-sheet (β7), followed by a seventh α-helix (α7), followed by an eighth β-sheet (β8), followed by an eighth α-helix (α8), followed by a ninth β-sheet (β9), followed by a ninth α-helix (α9), followed by a tenth β-sheet (α10), followed by a second inter-domain hinge segment (h2), followed by a tenth α-helix (α10), followed by a third inter-domain hinge segment (h3), followed by an eleventh β-sheet (β11). In some embodiments, the polypeptide comprises (i) 1, 2, or 3 amino acid substitutions between β1 and α1; (ii) 1, 2, or 3 amino acid substitutions between β2 and α2; (iii) 1, 2, or 3 amino acid substitutions between the β3 and α3; (iv) 1, 2, or 3 amino acid substitutions between the β4 and α4; (v) 1, 2, or 3 amino acid substitutions in β6; (vi) 1, 2, or 3 amino acid substitutions in α6; (vii) 1, 2, or 3 amino acid substitutions between the β7 and α7; (viii) 1, 2, or 3, amino acid substitutions in α8; and/or (ix) 1, 2, or 3 amino acid substitutions between the β9 and α9. In some embodiments, the substitutions are conservative substitutions. In various embodiments, the polypeptide comprises a cysteine substitution at β7, α7, or between β7 and α7.

The glucose-galactose binding polypeptide may further comprise 1, 2, or more Ca²⁺ binding sites.

In various embodiments, the C_(α) root-mean-square deviation (RMSD) between the backbone of the glucose-galactose binding polypeptide and ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, and/or chyGGBP is, e.g., between about 0.1-3 Å, 0.5-1 Å, 0.5-1.5 Å, or 0.5-2 Å, or less than about 0.1 Å, 0.2 Å, 0.3 Å, 0.4 Å, 0.5 Å, 0.6 Å, 0.7 Å, 0.8 Å, 0.9 Å, 1.0 Å, 1.5 Å, 1.6 Å, 1.7 Å, 1.8 Å, 1.9 Å, 2.0 Å, 2.5 Å, or 3 Å. In some embodiments, the C_(α) RMSD between the N-terminal domain (i.e., the portion of the protein at the N-terminal side of the binding domain hinge) backbone of the glucose-galactose binding polypeptide and the corresponding domain of ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, and/or pspGGBP is, e.g., between about 0.1-3 Å, 0.5-1 Å, 0.5-1.5 Å, or 0.5-2 Å, or less than about 0.1 Å, 0.2 Å, 0.3 Å, 0.4 Å, 0.5 Å, 0.6 Å, 0.7 Å, 0.8 Å, 0.9 Å, 1.0 Å, 1.5 Å, 1.6 Å, 1.7 Å, 1.8 Å, 1.9 Å, 2.0 Å, 2.5 Å, or 3 Å. In certain embodiments, the C_(α) RMSD between the C-terminal domain (i.e., the portion of the protein at the C-terminal side of the binding domain hinge) backbone of the glucose-galactose binding polypeptide and the corresponding domain of ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, and/or chyGGBP is, e.g., between about 0.1-3 Å, 0.5-1 Å, 0.5-1.5 Å, or 0.5-2 Å, or less than about 0.1 Å, 0.2 Å, 0.3 Å, 0.4 Å, 0.5 Å, 0.6 Å, 0.7 Å, 0.8 Å, 0.9 Å, 1.0 Å, 1.5 Å, 1.6 Å, 1.7 Å, 1.8 Å, 1.9 Å, 2.0 Å, 2.5 Å, or 3 Å. Non-limiting considerations relating to the sequence and structural differences between homologous proteins are discussed in Chothia and Lesk (1986) The EMBO Journal, 5(4):823-826, the entire content of which is incorporated herein by reference.

Non-limiting examples of glucose-galactose binding polypeptides that are useful in biosensors provided herein include ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, and chyGGBP. In embodiments, a biosensor comprises a modified ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, or chyGGBP polypeptide having an amino acid substitution compared to its naturally occurring counterpart, such that the polypeptide has a cysteine at position 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, or 383 or any combination of 1, 2, 3, 4, or 5 thereof, wherein the position corresponds a SEQ ID NO disclosed herein for ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, or chyGGBP. In embodiments, the cysteine is conjugated to a reporter group.

In embodiments, a biosensor comprises a modified ecGGBP. In non-limiting examples, the modified ecGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Y10X, D14X, N15X, F16X, P70X, N91X, K92X, S112X, S115X, E149X, H152X, P153X, D154X, A155X, R158X, M182X, W183X, N211X, D212X, D236X, L238X, D257X, P294X, and V296X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in ecGGBP without including the signal peptide (SEQ ID NO: 17). In some embodiments, the modified ecGGBP comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 of the following substitutions: Y10A, Y10C, D14C, D14A, D14Q, D14N, D14S, D14T, D14E, D14H, D14L, D14Y, D14F, F16L, F16A, F16C, N91C, N91A, K92A, K92C, E149C, E149K, E149Q, E1495, H152C, H152A, H152F, H152Q, H152N, D154C, D154A, D154N, A155C, A1555, A155H, A155L, A155F, A155Y, A155N, A155K, A155M, A155W, A155Q, R158C, R158A, R158K, M182C, M182W, W183C, N211C, N211F, N211W, N211K, N211Q, N2115, N211H, N211M, N211C, D212C, L238C, D236C, D236A, D236N, N256A, N256D, D257C, P294C, and V293C.

In various embodiments, a biosensor comprises a modified ttGGBP. In non-limiting examples, the modified ttGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Y11X, D15X, T16X, F17X, G20X, N42X, V67X, R69X, R91X, E92X, A111X, Q148X, H151X, Q152X, A154X, N181X, W182X, D183X, D211X, T237X, T240X, L257X, N258X, D259X, A260X, and K300X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in ttGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 18). In some embodiments, the modified ttGGBP comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 of the following substitutions: Y11C, D15A, D15E, D15N, D15C, T16S, T16N, T16C, F17C, G20A, G20C, N42C, V67C, R69P, R69C, R91K, E92C, A111C, Q148S, Q148K, Q148E, Q148C, H151Q, H151N, H151F, H151C, Q152P, Q152C, A154S, A154N, A154M, A154F, A154C, N181C, W182C, D183C, D211A, D211C, T237C, T240A, L257C, N258D, N258S, N258A, N258C, D259C, A260N, A260Q, A260R, A260K, A260W, A260F, A260Y, A260S, A260C, and K300C.

In embodiments, a biosensor comprises a modified stGGBP. In non-limiting examples, the modified stGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Y11X, Y13X, D15X, N16X, F17X, P71X, N92X, K93X, P113X, S116X, E150X, H153X, P154X, D155X, A156X, R159X, M183X, W184X, N211X, N212X, D213X, A214X, D237X, L239X, D258X, P295X, and V297X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in stGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 19). In some embodiments, the modified stGGBP comprises 1, 2 or 3 of the following mutations: Y13C, F17C, and W184C.

In embodiments, a biosensor comprises a modified chyGGBP. In non-limiting examples, the modified chyGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F12X, D14X, T15X, F16X, R68X, N89X, R90X, A110X, S113X, E147X, H150X, Q151X, D152X, A153X, R156X, M180X, W181X, N207X, N208X, D209X, D210X, D237X, T239X, D258X, V296X, and Y298X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in chyGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 20). In some embodiments, the modified chyGGBP comprises 1, 2, or 3 of the following mutations: F12C, F16C, C39A, W181C, and C206A.

In embodiments, a biosensor comprises a modified cobGGBP. In non-limiting examples, the modified cobGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F12X, D14X, T15X, F16X, C39X, R68X, N89X, R90X, A110X, S113X, E147X, H150X, Q151X, D152X, A153X, R156X, C173X, M180X, W181X, C206X, N207X, N208X, D209X, D210X, D237X, T239X, D258X, P297X, and Q299X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in cobGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 21). In some embodiments, the modified cobGGBP comprises 1, 2, or 3 of the following mutations: F12C, F16C, C39A, C173A, W181C, and C206A.

In embodiments, a biosensor comprises a modified pspGGBP. In non-limiting examples, the modified pspGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F9X, D11X, T12X, F13X, R65X, N86X, R87X, A107X, S110X, E144X, H147X, Q148X, D149X, A150X, R153X, M177X, W178X, N204X, N205X, D206X, D207X, D234X, T236X, 255X, A294X, and K296X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in pspGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 22). In some embodiments, the modified pspGGBP comprises 1, 2, or 3 of the following mutations: F9C, F13C, and W178C.

In embodiments, a biosensor comprises a modified csaGGBP. In non-limiting examples, the modified csaGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Y14X, D16X, F18X, C62X, I72X, C82X, N93X, R94X, C113A, S118X, A121X, E152X, N155X, E156X, D157X, S158X, R161X, N185X, W186X, C211X, D241X, L243X, D262X, D290X, I292X, I297X, F299X, Q301X, and T302X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in csaGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 23). In some embodiments, the modified csaGGBP comprises 1, 2, 3, 4, 5, 6, 7, or 8 of the following mutations: Y14C, F18C, C62A, C82A, C113A, W186C, and C211A.

In embodiments, a biosensor comprises a modified bprGGBP. In non-limiting examples, the modified bprGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: C8X, K12X, D14X, N15X, F16X, S72X, N93X, R94X, C112X, C116X, A118X, S121X, A153X, N156X, I157X, D158X, A159X, C179X, N186X, W187X, C211X, N212X, N213X, D214X, A215X, D241X, D243X, K251X, C289X, D290X, and V292X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in bprGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 24). In some embodiments, the modified bprGGBP comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of the following mutations: CBA, K12C, F16C, C112A, C116A, C179A, W187C, C211A, and C289A.

In embodiments, a biosensor comprises a modified rinGGBP_A. In non-limiting examples, the modified rinGGBP_A may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: C6X, F10X, D12X, N13X, F14X, S70X, N91X, R92X, C114X, A116X, Q118X, D151X, N154X, V155X, D156X, A157X, R160X, C177X, N184X, W185X, C210X, N211X, N212X, D213X, A214X, D240X, L242X, L250X, C288X, D289X, and V291X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in rinGGBP_A with the signal peptide replaced with a methionine (SEQ ID NO: 25). In some embodiments, the modified rinGGBP_A comprises 1, 2, 3, 4, 5, 6, 7, or 8 of the following mutations: C6A, F10C, F14C, C114A, C177A, W185C, C210A, and C288A.

In embodiments, a biosensor comprises a modified rinGGBP_B. In non-limiting examples, the modified rinGGBP_B may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Q13X, D15X, T16X, F17X, C66X, C70A, R76X, N97X, R98X, A118X, S121X, E155X, H158X, Q159X, D160X, A161X, R164X, N188X, W189X, N215X, N216X, D217X, D218X, D244X, T246X, D265X, P301X, A303X, and C306X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in rinGGBP_B with the signal peptide replaced with a methionine (SEQ ID NO: 29). In some embodiments, the modified rinGGBP_B comprises 1, 2, 3, 4, 5, or 6 of the following mutations: Q13C, F17C, C66A, C70A, W189C, and C306A.

In embodiments, a biosensor comprises a modified fprGGBP. In non-limiting examples, the modified fprGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: C8A, F12X, D14X, N15X, F16X, T69X, N90X, R91X, C105X, C106X, A113X, S116X, C143X, D146X, N149X, I150X, D151X, A152X, R155X, N179X, W180X, C205A, N206X, N207X, D208X, A209X, D235X, L237X, N243X, D284X, and V286X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in fprGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 26). In some embodiments, the modified fprGGBP comprises 1, 2, 3, 4, 5, 6, or 7 of the following mutations: C8A, F12C, F16C, C105A, C106A, C143A, W180C, and C205A.

In embodiments, a biosensor comprises a modified cljGGBP. In non-limiting examples, the modified cljGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F11x, N13X, T14X, W15X, V67X, C77X, N88X, R89X, A109X, S112X, E142X, N145X, Q146X, D147X, A148X, R151X, M175X, W176X, C198X, N201X, N202X, D203X, D204X, D231X, T233X, D252X, D291X, and K294X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in cljGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 27). In some embodiments, the modified cljGGBP comprises 1, 2, 3, 4, or 5 of the following mutations: F11C, W15C, C77A, W176C, and C198A.

In embodiments, a biosensor comprises a modified cauGGBP. In non-limiting examples, the modified cauGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F12X, N14X, T15X, W16X, V68X, C78X, N89X, R90X, A110X, S113X, E143X, N146X, Q147X, D148X, A149X, R152X, M176X, W177X, C199X, N203X, N204X, D205X, D206X, D233X, T235X, D254X, D293X, and K295X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in cauGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 28). In some embodiments, the modified cauGGBP comprises 1, 2, 3, 4, or 5 of the following mutations: F12C, W16C, C78A, W177C, and C199A.

In embodiments, a biosensor comprises a modified erhGGBP. In non-limiting examples, the modified erhGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: F13X, D15X, N16X, F17X, P76X, N97X, R98X, A119X, S122X, D153X, N156X, V157X, D158X, A159X, R162X, M187X, W188X, N214X, N215X, D216X, G217X, D243X, I245X, D264X, E312X, and V314X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in erhGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 30). In some embodiments, the modified erhGGBP comprises 1, 2, or 3 of the following mutations: F13C, F17C, and W188C.

In embodiments, a biosensor comprises a modified ereGGBP. In non-limiting examples, the modified ereGGBP may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: Q13X, D15X, T16X, F17X, C29X, C65X, C69X, R75X, N96X, R97, A117X, S120X, E154X, H157X, Q158X, D159X, A160X, R163X, C183X, N187X, W188X, N214X, N215X, D216X, A217X, D243X, T245X, D264X, P301X, and E303X where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in ereGGBP with the signal peptide replaced with a methionine (SEQ ID NO: 31). In some embodiments, the modified ereGGBP comprises 1, 2, 3, 4, 5, 6, 7, or 8 of the following mutations: C10A, Q13C, F17C, C29A, C65A, C69A, C183A, and W188C.

In various embodiments, the mutant glucose-galactose binding polypeptide's glucose and/or galactose disassociation constant differs by at least about 1 μM, 5 μM, 10 μM, 20 μM, 25 μM, 30 μM, 35 μM, 40 μM, 45 μM, 50 μM, 75 μM, 100 μM, 200 μM, 300 μM, 400 μM, 500 μM, 600 μM, 700 μM, 800 μM, 900 μM, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 60 mM, 70 mM, 80 mM, 90 mM, or 100 mM (increase or decrease) compared to its naturally occurring counterpart.

The biosensors and ligand-binding proteins provided herein are robust and useful at a wide range of physical conditions, e.g., pressure, temperature, salinity, osmolality, and pH conditions. For example, biosensors and ligand-binding proteins provided herein may survive substantial periods of time after being dried or exposed to high temperatures. In some embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after exposure to a temperature of about 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, or 125, or 40-125° C. for about 1, 2, 3, 4, 5, 6, 15, 30, 60, 120, 180, 240, or 360 minutes. In certain embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after 1, 2, 3, 4, or 5 freeze-thaw cycles in an aqueous solution. In various embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after storage at a temperature of between 20-37° C. for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, or 1-24 months in dry form. In some embodiments, the optimal functional temperature of the biosensor is between 41 and 122° C., between 20 and 40° C., or less than about 10° C. (e.g., between −20 and +10° C.). Devices, compositions, and biosensors provided herein may be stored, e.g., with or without protection from exposure to light. In some embodiments, the devices, compositions, and biosensors are stored in the dark, e.g., with protection from light.

Reporter Group Attachment

Aspects of the present subject matter provide a biosensor that comprises a one or more reporter groups attached to a ligand-binding protein, wherein binding of a ligand to a ligand-binding domain of the ligand-binding protein causes a change in signaling by the reporter group. In various embodiments, the reporter group is attached to an endosteric site, an allosteric site, or a peristeric site of the ligand-binding protein. In embodiments, the reporter group is covalently or noncovalently attached to the ligand-binding protein.

For convenience and depending on context, a reporter group may be referred to by a name of an unattached form of the reporter group regardless of whether the reporter group is attached to a ligand-binding protein. For example, a compound known as “Compound A” when in an unconjugated form may be referred to herein as “Compound A” when in a form that is attached to a ligand-binding protein. In a specific example, the term “Acrylodan” is used to refer to unreacted/unconjugated Acrylodan, as well as Acrylodan that is conjugated to a ligand-binding protein.

In certain embodiments, a biosensor comprises a reporter group that is conjugated to a ligand-binding protein, and the reporter group is conjugated to an amino acid of the protein that is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 4, 6, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 angstroms (Å) from the ligand when the ligand is bound to the protein. In some embodiments, the reporter group is conjugated to an amino acid of the protein that is within an α-helix or a β-sheet. In some embodiments, the reporter group is conjugated to an amino acid that (i) is not within an α-helix or a β-sheet, but is within about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acids of an amino acid of the protein's amino acid sequence that is within α-helix or β-sheet. In some embodiments, the reporter group is conjugated to an amino acid that is in an inter-domain hinge amino acid region between two domains of a protein. In some embodiments, the reporter group is conjugated to an amino acid that is in an inter-domain hinge amino acid region between (i) α-helix and a β-sheet; (ii) two α-helixes; or (iii) two β-sheets of a protein. In some embodiments, the reporter group is conjugated to an amino acid (e.g., a cysteine such as a cysteine added by substitution compared to a naturally corresponding polypeptide) between positions 1-25, 25-50, 50-75, 75-100, 100-125, 125-150, 150-175, 175-200, 200-225, 225-250, 250-275, 275-350, 275-300, 275-325, 300-325, 300-350, 300-383, or 350-383 (inclusive) of a polypeptide (e.g., not including N-terminal fusion proteins compared to the polypeptide's naturally occurring counterpart).

Direct signaling relationships between proteins and reporter groups are readily designed by replacing a residue known to form a ligand contact with a cysteine to which the fluorophore is attached (“endosteric” attachment site). Other, indirect signaling relationships can be established in two ways. The first relies on visual inspection of the ligand complex structure, and identifying residues that are located in the vicinity of the binding site, but do not interact directly with the ligand, and that are likely to be involved in conformational changes. Typically, such “peristeric” sites are located adjacent to the residues that form direct contacts with the bound ligand. In the case of the bPBPs, such residues are located at the perimeter of the inter-domain cleft that forms the ligand binding site. The environment of these peristeric sites changes significantly upon formation of the closed state. These are examples of positions which are proximal to the ligand-binding pocket/domain. The second, most general, approach identifies sites in the protein structure that are located anywhere in the protein, including locations at some distance away from the ligand-binding site (i.e., distal to the ligand-binding pocket/domain), and undergo a local conformational change in concert with ligand binding. If the structures of both the open and closed states are known, then such “allosteric” sites can be identified using a computational method that analyzes the conformational changes that accompany ligand binding (Marvin et al., Proc. Natl. Acad. Sci. USA 94:4366-4371, 1997). Alternatively, once allosteric sites have been identified in one bPBP, modeling and structural homology arguments can be invoked to identify such sites in other bPBPs in which only one state has been characterized (Marvin & Hellinga, J. Am. Chem. Soc. 120:7-11, 1998). This generalized conformational analysis also may identify peristeric and endosteric sites, which were identified and classified by visual inspection.

In non-limiting implementations, the reporter group is attached to said ligand-binding protein via a biotin-avidin interaction. The reporter group may be, e.g., conjugated to biotin and the ligand-binding protein is conjugated to avidin. In an example, the avidin is bound to four biotin molecules wherein each biotin molecule is individually conjugated to a reporter group. Alternatively, the reporter group is conjugated to avidin and the ligand-binding protein is conjugated to biotin. For example, the avidin is bound to four biotin molecules, wherein each biotin molecule is individually conjugated to a ligand-binding protein.

As used herein, “conjugated” means covalently attached. One compound may be directly conjugated to another compound, or indirectly conjugated, e.g., via a linker.

In some embodiments, the reporter group is directly attached to said ligand-binding protein. In various embodiments, the reporter group is attached to an amino acid of the ligand-binding protein that is at least about 2, 4, 6, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 angstroms (Å) from the ligand when the ligand is bound to the ligand-binding protein. In certain embodiments, the reporter group is conjugated to an amino acid having a position within positions 1-25, 25-50, 50-75, 75-100, 100-125, 125-150, 150-175, 175-200, 200-225, 225-250, 250-275, or 275-300 of the ligand-binding protein, wherein position 1 is the N-terminal amino acid of the ligand-binding protein. In non-limiting examples, the reporter group is conjugated to an amino acid of the ligand-binding protein that is (a) within an α-helix or a β-sheet of the ligand-binding protein; (b) not within an α-helix; (c) not within a β-sheet; (d) within about 5 or 10 amino acids of an amino acid that is within an α-helix or β-sheet; (e) within a stretch of consecutive amino acids that links two domains of the ligand-binding protein; (f) within a stretch of consecutive amino acids that links an α-helix and a β-sheet; (g) within a stretch of consecutive amino acids that links two α-helices; or (h) within a stretch of consecutive amino acids that links two β-sheets. In some embodiments, the reporter group is directly attached to the N-terminus or the C-terminus of the ligand-binding protein.

The reporter group may be conjugated to the ligand-binding protein a variety of linkers or bonds, including (but not limited to) a disulfide bond, an ester bond, a thioester bond, an amide bond, or a bond that has been formed by a click reaction. In some embodiments, the click reaction is a reaction between (a) an azide and an alkyne; (b) an azide and an alkyne in the presence of Cu(I); (c) an azide and a strained cyclooctyne; (d) an azide and a dibenzylcyclooctyne, a difluorooctyne, or a biarylazacyclooctynone; (e) a diaryl-strained-cyclooctyne and a 1,3-nitrone; (f) an azide, a tetrazine, or a tetrazole and a strained alkene; (g) an azide, a tetrazine, or a tretrazole and a oxanorbornadiene, a cyclooctene, or a trans-cycloalkene; (h) a tetrazole and an alkene; or (i) a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene. These exemplary click chemistry reactions have high specificity, efficient kinetics, and occur in vivo under physiological conditions. See, e.g., Baskin et al. Proc. Natl. Acad. Sci. USA 104(2007):16793; Oneto et al. Acta biomaterilia (2014); Neves et al. Bioconjugate chemistry 24(2013):934; Koo et al. Angewandte Chemie 51(2012):11836; Rossin et al. Angewandte Chemie 49(2010):3375, and U.S. Patent Application Publication No. 20160220686, published Aug. 4, 2016, the entire content of each of which is incorporated herein by reference. For a review of a wide variety of click chemistry reactions and their methodologies, see e.g., Nwe K and Brechbiel M W, 2009 Cancer Biotherapy and Radiopharmaceuticals, 24(3): 289-302; Kolb H C et al., 2001 Angew. Chem. Int. Ed. 40: 2004-2021. The entire contents of each of the foregoing references are incorporated herein by reference.

As used herein, the term “linker” refers to a molecule or sequence (such as an amino acid sequence), that attaches, as in a bridge, one molecule or sequence to another molecule or sequence. “Linked” means attached or bound by covalent bonds, or non-covalent bonds, or other bonds, such as van der Waals forces. In some embodiments, a linker comprises a chemical structure that has resulted from a reaction used to attach one molecule to another.

In various implementations of the present subject matter, the reporter group is conjugated to a cysteine of the ligand-binding protein. The cysteine may be present on a natural counterpart or version of the ligand-binding protein or added to the ligand-binding protein by a substitution mutation. In some embodiments, the cysteine is at the N-terminus or the C-terminus of said ligand-binding protein.

Non-limiting examples relate to the conjugation of a reporter group to a primary amine of the ligand-binding protein. In certain embodiments, the primary amine is present in a lysine of said ligand-binding protein. The lysine may be present on a natural counterpart or version of the ligand-binding protein or added to the ligand-binding protein by a substitution mutation. In various embodiments, the lysine is at the N-terminus or the C-terminus of the ligand-binding protein.

Aspects of the present subject matter provide a biosensor in which the reporter group is attached to the ligand-binding protein via a linker. In some embodiments, the linker comprises an organic compound that is less than about 30, 20, 15, or 10 Å long. Non-limiting examples of spacers include O, S, NH, PH, and alkyl spacers.

“Alkyl,” as used herein, refers to the radical of saturated or unsaturated aliphatic groups, including straight-chain alkyl, alkenyl, or alkynyl groups, branched-chain alkyl, alkenyl, or alkynyl groups, cycloalkyl, cycloalkenyl, or cycloalkynyl (alicyclic) groups, alkyl substituted cycloalkyl, cycloalkenyl, or cycloalkynyl groups, and cycloalkyl substituted alkyl, alkenyl, or alkynyl groups. Unless otherwise indicated, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C₁-C₃₀ for straight chain, C₃-C₃₀ for branched chain), more preferably 20 or fewer carbon atoms, more preferably 12 or fewer carbon atoms, and most preferably 8 or fewer carbon atoms. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure. The ranges provided above are inclusive of all values between the minimum value and the maximum value. The term “alkyl” includes both “unsubstituted alkyls” and “substituted alkyls,” the latter of which refers to alkyl moieties having one or more substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents include, but are not limited to, halogen, hydroxyl, carbonyl (such as a carboxyl, alkoxycarbonyl, formyl, or an acyl), thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, a phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. Unless the number of carbons is otherwise specified, “lower alkyl” as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure. Likewise, “lower alkenyl” and “lower alkynyl” have similar chain lengths. Preferred alkyl groups are lower alkyls. The alkyl groups may also contain one or more heteroatoms within the carbon backbone. Preferably the heteroatoms incorporated into the carbon backbone are oxygen, nitrogen, sulfur, and combinations thereof. In certain embodiments, the alkyl group contains between one and four heteroatoms.

In some embodiments, the linker comprises a bond formed by a chemical reaction involving a reactive group such as a maleimide group. Alternatively or in addition, the linker comprises a stretch of amino acids. In a non-limiting example, the linker comprises a polyglycine linker. In embodiments, the polyglycine linker comprises 2, 3, 4, 5, or more glycines. Optionally, the polyglycine linker further comprises a serine.

In various implementations, the reporter group is attached to a linker via a covalent bond and the linker is attached to a ligand-binding protein via a covalent bond. In embodiments, the covalent bond between the linker and the reporter group and/or the covalent bond between the linker and the ligand-binding protein is a disulfide bond, an ester bond, a thioester bond, an amide bond, a carbamate bond, or a bond that has been formed by a click reaction. Non-limiting examples of click reactions include reactions between an azide and an alkyne; an azide and an alkyne in the presence of Cu(I); an azide and a strained cyclooctyne; an azide and a dibenzylcyclooctyne, a difluorooctyne, or a biarylazacyclooctynone; a diaryl-strained-cyclooctyne and a 1,3-nitrone; an azide, a tetrazine, or a tetrazole and a strained alkene; an azide, a tetrazine, or a tretrazole and a oxanorbornadiene, a cyclooctene, or a trans-cycloalkene; a tetrazole and an alkene; or a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene.

Reporter Groups

Various types of reporter groups may be used in embodiments of the present subject matter. For example, the reporter group may comprise a fluorophore that produces a fluorescent signal. Biosensors comprising a fluorophore may be referred to herein as fluorescently responsive sensors (FRSs).

Preferably, the binding of ligand to an FRS results in a change in ratiometric ΔR in the signal from a reporter group. A ratiometric signal (R_(1,2)) is defined as the quotient of two intensities, I_(λ1) and λ_(λ2), measured at two independent wavelengths, λ₁ and λ₂ and may be calculated according to the following equation:

R _(1,2) =I _(λ1) /I _(λ2)

In some embodiments, intensities are integrated over a range of wavelengths in a recorded emission spectrum. In some embodiments, intensities are integrated over 10-nm, 15-nm, 20-nm, 25-nm, 30-nm, 35-nm, 40-nm, 45-nm, 50-nm, 75-nm, 100-nm, 10-40-nm, 10-50-nm, 20-50-nm, or 10-100-nm regions, centered between 400-800nm, e.g. between 420 nm and 520 nm for λ₁, and 400-800 nm, e.g. between 500 nm to 600 nm for λ₂. In some embodiments, intensities are recorded through a bandpass filter. A non-limiting example of a bandpass filter is a 10-nm, 15-nm, 20-nm, 25-nm, 30-nm, 35-nm, 40-nm, 45-nm, 50-nm, 75-nm, 100-nm, 10-40-nm, 10-50-nm, 20-50-nm, or 10-100-nm bandpass filter, centered between 400-800nm, e.g. at 452 nm for λ₁ and at 400-800nm, e.g. at 528 nm (λ₂).

Aspects of the present subject matter provide FRSs whose emission spectra change (e.g., the shape of the emission spectra change) in response to ligand binding. In various embodiments, the ratio of intensities at two chosen wavelengths of an FRS's emission spectrum changes upon ligand binding. In some embodiments, the emission wavelength and/or intensity of the fluorophore changes when the position of atoms within the fluorophore changes with respect to each other (e.g., due to the rotation of bound atoms with respect to each other or a change in the angle of a bond). In non-limiting examples, the emission wavelength and/or intensity of the fluorophore changes when (i) one portion of the fluorophore rotates around a bond axis compared to another portion of the fluorophore and/or (ii) when the angle of a bond between two atoms of said fluorophore changes. In a non-limiting example, the fluorophore is a prodan-derived fluorophore (e.g., Acrylodan or Badan) and binding of ligand alters the orientation of a dimethylamino group, a naphthalene ring, and/or a carbonyl with respect to the ligand-binding protein and/or each other. In a non-limiting example, the degree of polarization of a dipole on the fluorophore changes in response to ligand binding. In various embodiments, the emission wavelength and/or intensity of the fluorophore changes when an atom electrostatically interacts with said fluorophore. For example, the emission wavelength and/or intensity of the fluorophore changes when the source of a positive or negative charge changes its distance with respect to the fluorophore within about 1, 2, 3, 4, 5, or 10 Å of the fluorophore. In some embodiments, the fluorophore exhibits hypsochromicity or bathochromicity upon ligand binding to the ligand-binding domain of the ligand-binding protein. In certain embodiments, the fluorophore has an emission wavelength comprising a wavelength of about 550 nanometers (nm), 575 nm, 600 nm, 625 nm, 650 nm, or 550-650 nm.

In some embodiments, the signal comprises the emission intensity of the fluorophore recorded at a single wavelength or range of wavelengths. The change in signal may be a shift in the single wavelength or range of wavelengths. In some embodiments, the shift in the wavelength is at least about 1 nm, at least about 2 nm, at least about 3 nm, at least about 4 nm, at least about 5 nm, at least about 6 nm, at least about 7 nm, at least about 8 nm, at least about 9 nm, at least about 10 nm, at least about 11 nm, at least about 12 nm, at least about 13 nm, at least about 14 nm, at least about 15 nm, at least about 16 nm, at least about 17 nm, at least about 18 nm, at least about 19 nm, at least about 20 nm, at least about 25 nm, at least about 30 nm, at least about 35 nm, at least about 40 nm, at least about 45 nm, at least about 50 nm, at least about 55 nm, at least about 60 nm, at least about 65 nm, at least about 70 nm, at least about 75 nm, at least about 80 nm, at least about 85 nm, at least about 90 nm, at least about 95 nm, at least about 100 nm, at least about 105 nm, at least about 110 nm, at least about 115 nm, at least about 120 nm, at least about 125 nm, or at least about 130 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm, about 2 nm to about 20 nm, about 3 nm to about 20 nm, about 4 nm to about 20 nm, about 5 nm to about 20 nm, about 1 nm to about 19 nm, about 1 nm to about 18 nm, about 1 nm to about 17 nm, 1 nm to about 16 nm, about 1 nm to about 15 nm, about 1 nm to about 14 nm, about 1 nm to about 13 nm, about 1 nm to about 12 nm, about 1 nm to about 11 nm, or about 1 nm to about 10 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 130 nm.

In certain embodiments, the signal comprises the ratio or quotient of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths, i. e. , a ratiometric signal. For example, as shown in FIGS. 1A-C, ligand binding may be determined by measuring the ratio of blue to green emission intensities. The change in signal may be decreased emission intensity at one wavelength, and no change in emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and no change in emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and increased emission intensity at the other wavelength. The change in signal may be decreased emission intensity at one wavelength, and decreased emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and decreased emission intensity at the other wavelength. In some embodiments, the change in ratio of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths may be at least about 1.1-fold, at least about 1.2-fold, at least about 1.4-fold, at least about 1.6-fold, at least about 1.8-fold, at least about 2.0-fold, at least about 2.5-fold, at least about 3-fold, at least about 3.5-fold, at least about 4-fold, at least about 4.5-fold, at least about 5-fold, at least about 5.5-fold, at least about 6-fold, at least about 6.5-fold, at least about 7-fold, at least about 7.5-fold, at least about 8-fold, at least about 8.5-fold, at least about 9-fold, at least about 9.5-fold, at least about 10-fold, at least about 12-fold, at least about 14-fold, at least about 16-fold, at least about 18-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, at least about 50-fold, at least about 55-fold, at least about 60-fold, at least about 65-fold, at least about 70-fold, at least about 75-fold, at least about 80-fold, at least about 85-fold, at least about 90-fold, at least about 95-fold, or at least about 100-fold. In some embodiments, the change in ratio of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths may be a decrease of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or of 5-25%, 25-50%, 25-75%, 50-75%, 50-90%, or 75-99% or the reciprocal thereof.

The change in signal may be a change in the ratio of the two distinct wavelengths or ranges of wavelengths. The change in signal may be a shift in the two distinct wavelengths or ranges of wavelengths. In some embodiments, one wavelength shifts. In some embodiments, both wavelengths shift. In some embodiments, the shift in the wavelength is at least about 1 nm, at least about 2 nm, at least about 3 nm, at least about 4 nm, at least about 5 nm, at least about 6 nm, at least about 7 nm, at least about 8 nm, at least about 9 nm, at least about 10 nm, at least about 11 nm, at least about 12 nm, at least about 13 nm, at least about 14 nm, at least about 15 nm, at least about 16 nm, at least about 17 nm, at least about 18 nm, at least about 19 nm, at least about 20 nm, at least about 25 nm, at least about 30 nm, at least about 35 nm, at least about 40 nm, at least about 45 nm, at least about 50 nm, at least about 55 nm, at least about 60 nm, at least about 65 nm, at least about 70 nm, at least about 75 nm, at least about 80 nm, at least about 85 nm, at least about 90 nm, at least about 95 nm, at least about 100 nm, at least about 105 nm, at least about 110 nm, at least about 115 nm, at least about 120 nm, at least about 125 nm, or at least about 130 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm, about 2 nm to about 20 nm, about 3 nm to about 20 nm, about 4 nm to about 20 nm, about 5 nm to about 20 nm, about 1 nm to about 19 nm, about 1 nm to about 18 nm, about 1 nm to about 17 nm, 1 nm to about 16 nm, about 1 nm to about 15 nm, about 1 nm to about 14 nm, about 1 nm to about 13 nm, about 1 nm to about 12 nm, about 1 nm to about 11 nm, or about 1 nm to about 10 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 130 nm.

A fluorophore may comprise, e.g., a fluorescent protein or an organic compound having a molecular weight less than about 2000 Daltons (Da). Non-limiting examples of commercially available fluorophores include such as 5-iodoacetamidofluorescein (SIAF) or 6-iodoacetamidofluorescein (6IAF), rhodamine, Oregon Green, eosin, Texas Red, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, Badan, Acrylodan, IAEDANS, comprising 3-cyano-7-hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy-4-methylcoumarin, or 7-amino-4-methylcoumarin, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, DRAQS, DRAQ7, or CyTRAK Orange, cascade blue, Nile red, Nile blue, cresyl violet, oxazine 170, proflavin, acridine orange, acridine yellow, auramine, crystal violet, malachite green, porphin, phthalocyanine, bilirubin, pyrene, N,N′-dimethyl-N-(iodoacetyl)-N′-(7-nitrobenz-2-ox-a-1,3-diazol-4-yl)ethylenediamide (NBD), N-((2-(iodoacetoxy)ethyl)-N-methy-1)amino-7-nitrobenz-2-oxa-1,3-diazole (NBDE), Acrylodan, JPW4039, JPW4042, JPW4045, Oregon Green, Pacific Blue, CPM, N,N′-Dimethyl-N-(Iodoacetyl)-N′-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Ethylenediamine (IANBD), 7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin (CPM), BODIPY 499, BODIPY 507/545, BODIPY 499/508, Alexa 432, Alexa488, Alexa532, Alexa546, Cy5, or 1-(2-maleimidylethyl)-4-(5-(4-methoxyphenyl)oxazol-2-yl)pyridinium methanesulfonate (PyMPO maleimide) (PyMPO). In various embodiments, the reporter group was thiol-reactive prior to being conjugated to a polypeptide disclosed herein. In embodiments, the reporter group is linked to a polypeptide disclosed herein via a disulfide bond. Additional non-limiting examples of commercially available fluorophores include fluorescent proteins such as Blue Fluorescent Protein (BFP), TagBFP, mTagBFP2, Azurite, Enhanced Blue Florescent Protein 2 (EBFP2), mKalamal, Sirius, Sapphire, T-Sapphire, Cyan Fluorescent Protein (CFP); Enhanced Cyan Fluorescent Protein (ECFP), Cerulean, SCFP3A, mTurquoise, mTurquoise2, monomeric Midoriishi-Cyan, TagCFP, mTFP1, AmCyan1, Green Fluorescent Protein (GFP), Enhanced Green Fluorescent Protein (EGFP), Emerald, Superfolder GFP, AcGFP1, ZsGreen1, Monomeric Azami Green, TagGFP2, mUKG, mWasabi, Clover, mNeonGreen, Yellow Fluorescent Protein (YFP), Enhanced Yellow Fluorescent Protein (EYFP), Citrine, Venus, Super Yellow Fluorescent Protein 2 (SYFP2), TagYFP, ZsYellow 1, mBanana, Orange Fluorescetn Protein (OFP), Monomeric Kusabira-Orange (mKO), mKOκ, mKO2, mOrange, mOrange2, Red Fluorescent Protein (RFP), DsRed-Express, DsRed-Express2, DsRed2, AsRed2, mRaspberry, mCherry, mStrawberry, mTangerine, tdTomato, TagRFP, TagRFP-T, mApple, mRuby, mRuby2, mPlum, HcRed-Tandem, mKate2, mNeptune, HcRed1, E2-Crimson, NirFP, TagRFP657, IFP1.4, or iRFP.

In some embodiments, the fluorophore comprises xanthene, a xanthene derivative, cyanine, a cyanine derivative, squaraine, a squaraine derivative, naphthalene, a naphthalene derivative, coumarin, a coumarin derivative, oxadiazole, an oxadiazole derivative, anthracene, an anthracene derivative, a boradiazaindacine (BODIPY) family fluorophore, pyrene, a pyrene derivative, acridine, an acridine derivative, arylmethine, an arylmethine derivative, tetrapyrrole, or a tetrapyrrole derivative. For example, the fluorophore may comprise a xanthene derivative comprising fluorescein or a fluorescein derivative, rhodamine, Oregon Green, eosin, or Texas Red. Non-limiting examples of fluorescein derivatives include 5-fluorescein, 6-carboxyfluorescein, 3′6-carboxyfluorescein, 5(6)-carboxyfluorescein, 6-hexachlorofluorescein, 6-tetrachlorofluorescein, or isothiocyanate. In some embodiments, the fluorophore comprises a cyanine derivative comprising indocarbocyanine, oxacarbocyanine, thiacarbocyanine, or merocyanine. In certain embodiments, the fluorophore comprises a squaraine derivative comprising a ring-substituted squaraine. In various embodiments, the fluorophore comprises a naphthalene derivative comprising a dansyl or prodan naphthalene derivative. In a non-limiting example, the fluorophore comprises prodan or a derivative thereof. In certain embodiments, the fluorophore comprises Badan, Acrylodan, or N-(Iodoacetaminoethyl)-1-naphthylamine-5-sulfonic acid (IAEDANS). In some embodiments, the fluorophore comprises a coumarin derivative such as 3-cyano-7-hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy-4-methylcoumarin (DiFMU), or 7-amino-4-methylcoumarin. In various embodiments, the fluorophore comprises an oxadiazole derivative such as pyridyloxazole, nitrobenzoxadiazole, or benzoxadiazole. In certain embodiments, the fluorophore comprises an anthracene derivative comprising an anthraquinone such as DRAQS, DRAQ7, or CyTRAK Orange. In various embodiments, the fluorophore comprises a pyrene derivative comprising cascade blue. In non-limiting examples the fluorophore comprises an oxazine derivative such as Nile red, Nile blue, cresyl violet, or oxazine 170. In some embodiments, the fluorophore comprises an acridine derivative such as proflavin, acridine orange, or acridine yellow. In certain embodiments, the fluorophore comprises an arylmethine derivative such as auramine, crystal violet, or malachite green. In various embodiments, the fluorophore comprises a tetrapyrrole derivative comprising porphin, phthalocyanine, or bilirubin.

Aspects of the present subject matter relate to the use of fluorophores that may readily be attached to a ligand-binding protein disclosed herein, e.g., at a cysteine residue. For example, a fluorophore may comprise a sulfhydryl group prior to attachment to a ligand-binding protein that is reacted with a moiety of the ligand-binding protein to attach the fluorophore to the ligand-binding protein. In some embodiments, the fluorophore comprised a thiol group prior to attachment to the ligand-binding protein. For example, the fluorophore was thiol reactive prior to attachment to said ligand-binding protein. Non-limiting examples of fluorophores that may readily be attached to ligand-binding proteins using thiol reactions include fluorescein, pyrene, NBD, NBDE, Acrylodan (6-acryloy 1-2-dimethylaminonaphthalene), Badan (6-bromo-acetyl-2-dimethylamino-naphthalene), JPW4039, JPW4042, or JPW4045.

In certain embodiments, the fluorophore comprises a derivative of a Prodan-based fluorophore such as Acrylodan or Badan. The excitation and emission properties of the Prodan-based fluorophores Acrylodan and Badan can be altered by manipulating the fluorescent ring system, while preserving the dimethylamino donor group, and the twistable carbonyl acceptor (Klymchenko 2013 Progress in Molecular Biology and Translational Science, 35-58). Replacement of the two-ring naphthalene with a three-ring anthracene (Lu 2006 J. Org. Chem., 71, 9651-9657), fluorene (Kucherak 2010 J. Phys. Chem. Lett., 1, 616-620), pyrene (Niko 2013 Chem. Eur. J., 19, 9760-9765), or styrene (Benedetti 2012 J. Am. Chem. Soc., 134, 12418-12421) cores significantly red-shift the excitation and emission properties, and in the case of the latter two, improve brightness through improvements in their excitation peak extinction coefficients. The entire content of each of the references cited above (as well as all other references referred to herein including the contents of nucleic acid and amino acid sequence accession number references) are incorporated herein by reference. Non-limiting examples of prodan analogues include 2-cyano-6-dihexylaminoanthracene and 2-propionyl-6-dihexylaminoanthracene, as well as fluorophores comprising the following structures:

In some embodiments, the fluorophore comprises a fluorescent protein. Fluorescent proteins that emit blue, cyan, green, yellow, orange, red, far-red, or near infrared radiation when contacted with excitation radiation are known in the art and commercially available as proteins and via the expression of vectors that encode the fluorescent protein. Non-limiting examples of fluorescent proteins include Blue Fluorescent Protein (BFP), TagBFP, mTagBFP2, Azurite, Enhanced Blue Florescent Protein 2 (EBFP2), mKalama1, Sirius, Sapphire, T-Sapphire, Cyan Fluorescent Protein (CFP); Enhanced Cyan Fluorescent Protein (ECFP), Cerulean, SCFP3A, mTurquoise, mTurquoise2, monomeric Midoriishi-Cyan, TagCFP, mTFP1, AmCyan1, Green Fluorescent Protein (GFP), Enhanced Green Fluorescent Protein (EGFP), Emerald, Superfolder GFP, AcGFP1, ZsGreenl, Monomeric Azami Green, TagGFP2, mUKG, mWasabi, Clover, mNeonGreen, Yellow Fluorescent Protein (YFP), Enhanced Yellow Fluorescent Protein (EYFP), Citrin, Venus, Super Yellow Fluorescent Protein 2 (SYFP2), TagYFP, ZsYellow1, mBanana, Orange Fluorescetn Protein (OFP), Monomeric Kusabira-Orange (mKO), mKOK, mKO2, mOrange, mOrange2, Red Fluorescent Protein (RFP), DsRed-Express, DsRed-Express2, DsRed2, AsRed2, mRaspberry, mCherry, mStrawberry, mTangerine, tdTomato, TagRFP, TagRFP-T, mApple, mRuby, mRuby2, mPlum, HcRed-Tandem, mKate2, mNeptune, HcRed1, E2-Crimson, NirFP, TagRFP657, IFP1.4, or iRFP.

In some embodiments, the fluorophore comprises a quantum dot (Medintz et al. 2005) (Sapsford, Berti and Medintz 2006 Angew Chem Int Ed Engl, 45, 4562-89; Resch-Genger et al. 2008 Nat Methods, 5, 763-75). In some embodiments the emission properties of the conjugated protein are enhanced by immobilization on or near metallic nanoparticles (Zeng et al. 2014 Chem Soc Rev, 43, 3426-52; Shen et al. 2015 Nanoscale, 7, 20132-41).

In various embodiments, the peak emission wavelength and/or the emission intensity of the biosensor change when the ligand binds to the ligand-binding protein. In some embodiments, the biosensor exhibits a dichromatic signaling change when the ligand binds to the ligand-binding protein. In various embodiments, the peak emission wavelength of the biosensor shifts by at least about 5, 10, 15, 20, 30, 40, 50, or by about 5-50 nm when the biosensor binds to ligand. In certain embodiments, the emission intensity of the biosensor increases by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, or 300% when the biosensor binds to ligand. In various embodiments, the signal produced by said reporter group persists for at least 1 nanoseconds (ns), 5 ns, 10 ns, 25 ns, 50 ns, 75 ns, 100 ns, 200 ns, 300 ns, 400 ns, 500 ns, 600 ns, 700 ns, 800 ns, 900 ns, 0.001 milliseconds (ms), 0.01 ms, 0.1 ms, 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, or 500 ms when the ligand binds to the ligand-binding protein.

Exemplary Methods of Using Biosensors Provided Herein

Aspects of the present subject matter provide a method of assaying for a ligand in a sample. The method may include contacting the sample with a biosensor disclosed herein under conditions such that the ligand-binding protein of the biosensor binds to the ligand if ligand is present in said sample. The method also comprises detecting (i) whether a signal is produced by a reporter group of the biosensor; and/or (ii) the a signal produced by a reporter group of the biosensor. In a non-limiting example, a reporter group of the biosensor is fluorescent, and the method further comprises contacting the reporter group with electromagnetic radiation having a wavelength that comprises a wavelength within the band of excitation wavelengths of the reporter group.

In various embodiments, the method further comprises (i) comparing a signal produced by a reporter group of the biosensor when the biosensor is contacted with the sample with a signal produced by a control sample containing a known quantity of ligand; and (ii) detecting the presence or absence of ligand in said sample based on this comparison. Alternatively or in addition, the method further comprises (i) comparing a signal produced by a reporter group of the biosensor when the biosensor is contacted with the sample with signals produced by a series of control samples containing known quantities of ligand; and (ii) determining the quantity of ligand in the sample based on this comparison. In some embodiments, the series of control samples comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 control samples, and wherein each control sample comprises a different quantity of ligand. Alternatively or in addition, the method further comprises determining the concentration of a ligand in a sample, wherein determining the concentration of the ligand in the sample comprises comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of the ligand in the test sample, wherein the standard hyperbolic ligand binding curve is prepared by measuring the signal produced by the reporter group of the biosensor when the biosensor is contacted with control samples containing known concentrations of ligand. In various embodiments, the method comprises (i) measuring a ratiometric change (ΔR) and/or an intensity change (ΔI) of a signal produced by the reporter group. In some embodiments, the method includes quantitating the level of ligand present in said sample.

In various embodiments, the ligand comprises glucose and/or galactose and said ligand-binding protein comprises a glucose-galactose binding protein.

Aspects of the present subject matter also provide a method of assaying for multiple ligands in a sample, wherein the multiple ligands comprise a first ligand and a second ligand. Such a method may include contacting the sample with (i) a first biosensor a first ligand provided herein and (ii) a second biosensor for said second ligand, under conditions such that the ligand-binding protein of said first biosensor binds to said first ligand, if said first ligand is present in said sample, and detecting (i) a signal produced by a reporter group of said first biosensor, or (ii) whether a signal is produced by a reporter group of said first biosensor. In some embodiments, the second biosensor is also a biosensor provided herein, and the second biosensor is contacted with the second ligand under conditions such that the ligand-binding protein of the second biosensor binds to the second ligand it is present in the sample. The method may further comprise detecting (i) a signal produced by a reporter group of the second biosensor, or (ii) whether a signal is produced by a reporter group of the second biosensor.

In some embodiments, the signal produced by the reporter group of said first biosensor is different than the signal produced by the reporter group of said second biosensor. In a non-limiting example, the reporter group of said first biosensor and the reporter group of said second biosensor are each fluorescent, and the peak emission wavelength of the reporter group of the first biosensor is at least about 10, 25, 50, 75, or 100 nm greater or lower than the peak emission wavelength of the reporter group of the second biosensor.

Non-limiting examples of biosensors that may be used as the second biosensor include biosensors with ligand-binding proteins comprising a GGBP (e.g., an E. coli GGBP) or a derivative or mutant thereof; (ii) an E. coli arabinose binding protein (e.g., an E. coli arabinose binding protein) or a derivative or mutant thereof; (iii) a dipeptide binding protein (e.g., an E. coli dipeptide binding protein) or a derivative or mutant thereof; (iv) a histidine binding protein (e.g., an E. coli, histidine binding protein) or a derivative or mutant thereof; (v) a ribose binding protein (e.g., an E. coli ribose binding protein) or a derivative or mutant thereof; (vi) a sulfate binding protein (e.g., an E. coli sulfate binding protein) or a derivative or mutant thereof; (vii) a maltose binding protein (e.g., an E. coli maltose binding protein) or a derivative or mutant thereof; (viii) a glutamine binding protein (e.g., an E. coli glutamine binding protein) or a derivative or mutant thereof; (ix) a glutamate/aspartate binding protein (e.g., an E. coli glutamate/aspartate binding protein) or a derivative or mutant thereof; (x) a phosphate binding protein (e.g., an E. coli phosphate binding protein) or a derivative or mutant thereof; or (xi) an iron binding protein [e.g., a Haemophilus influenza (H. influenzae) iron binding protein] or a derivative or mutant thereof. For example, the second biosensor comprises an E. coli GGBP having a Y10C, Y10A, D14A, D14Q, D14N, D14S, D14T, D14E, D14H, D14L, D14Y, D14F, N15C, F16L, F16A, F16Y, K92A, N91A, E93C, S112A, S115A, E149C, E149K, E149Q, E149S, H152A, H152F, H152Q, H152N, H152C, D154A, D154N, A155S, A155H, A155L, A155F, A155Y, A155N, A155K, A155M, A155W, A155Q, R158A, R158K, M182W, W183C, W183A, N211F, N211W, N211K, N211Q, N211S, N211H, N211M, D236A, D236N, L255C, N256A, N256D, D257C, P294C, or V296C mutation (e.g., comprising 1, 2, 3, 4, 5 or more of these mutations), wherein each amino acid position is numbered as in (SEQ ID NO: 17); (ii) an E. coli arabinose binding protein having a D257C, F23C, K301C, L253C, or L298C mutation (e.g., comprising 1, 2, 3, 4, or 5 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (iii) an E. coli dipeptide binding protein having a D450C, K394C, R141C, S111C, T44C, or W315C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (iv) an E. coli, histidine binding protein having a E167C, K229C, V163C, Y230C, F231C, Y88C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (v) an E. coli ribose binding protein having a T135C, D165C, E192C, A234C, L236C, or L265C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (vi) an E. coli sulfate binding protein having a L65C, N70C, Q294C, R134C, W290C, or Y67C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (vii) an E. coli maltose binding protein having a D95C, F92C, E163C, G174C, I329C, or S233C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (viii) an E. coli glutamine binding protein having a N160C, F221C, K219C, L162C, W220C, Y163C, or Y86C mutation (e.g., comprising 1, 2, 3, 4, 5 or more of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (ix) an E. coli glutamate/aspartate binding protein having a A207C, A210C, E119C, F126C, F131C, F270C, G211C, K268C, Q123C, or T129C mutation (e.g., comprising 1, 2, 3, 4, 5 or more of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (x) an E. coli phosphate binding protein having a A225C, N223C, N226C, S164C, or S39C mutation (e.g., comprising 1, 2, 3, 4, or 5 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); or (xi) a Haemophilus influenza (H. influenzae) iron binding protein having a E203C, K202C, K85C, or V287C mutation (e.g., comprising 1, 2, 3, or 4 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference). In various embodiments, the sample is suspected of comprising glucose or galactose.

References and PDB^(a) files for bPBP structures, genes, and ligand binding crystal structure bPBP open form closed form DNA sequence ligand affinity arabinose BP Quiocho and Scripture et al., Clark et al., Vyas, 1984 1ABE 1987 1982; Miller et al., 1983 dipeptide BP Nickitenko et Dunten & Abouhamad et Guyer et al., al., 1995 1DPE Mowbray, 1995 al., 1991 1986; Smith et 1DPP al., 1999 Glu/Asp BP Barash Halpern, 1975; Willis Furlong, 1975 Fe(III) BP Bruns et al., Bruns et al., 1997 Sanders et al., Adhikari et al., 2001 1D9V 1MRP 1994 1995 glucose BP Vyas et al., 1988; Scholle et al., Anraku, 1968 Vyas et al., 1994 1987 1GLG histidine BP Yao et al., 1994 Joshi & Ames Miller et al., 1HSL 1996 1983 maltose BP Sharff et al., Spurlino el al., Duplay et al., Schwartz et al., 1992 1OMP 1991; Quiocho et al., 1984 1976 1997 1ANF phosphate BP Ledvina et al., Luecke & Magota et al., Medveczky & 1996 1OIB Quiocho, 1990 1984 Rosenberg, 1969 1IXH glutamine BP Hsiao et al., Sun et al., 1998 Nohno et al., Weiner et al., 1996 1GGG 1WDN 1986 1971 ribose BP Bjorkman & Mowbray & Cole, Groarke et al., Willis & Mowbray, 1998 1992 2DRI 1983 Furlong, 1974 1URP sulfate BP Pflugrath & Hellinga & Jacobson & Quiocho, 1985; Evans, 1985 Quiocho, 1988 He & Quiocho, 1993 1SBP ^(a)Protein Data Bank (Berman et al., 2000) Abouhamad et al., Molec. Microbiol. 5: 1035-1047 (1991) Adhikari et al., J. Biol. Chem. 270: 25142-25149 (1995) Anraku, J. Biol. Chem. 243: 3116-3122 (1968) Barash & Halpern, Biochim. Biophys. Acta 386: 168-180 (1975) Bjorkman & Mowbray, J. Mol. Biol. 279: 651-664 (1998) Bruns et al., Biochemistry 40: 15631-15637 (2001) Bruns et al., Nat. Struct. Biol. 4: 919-924 (1997) Clark et al., Biochemistry 21: 2227-2233 (1982) Dunten & Mowbray, Protein Sci. 4: 2327-2334 (1995) Duplay et al., J. Biol. Chem. 259: 10606-10613 (1984) Groarke et al., J. Biol. Chem. 258: 12952-12956 (1983) Guyer et al., J. Bacteriol. 168: 775-779 (1986) He & Quiocho, Protein Sci. 2: 1643-1647 (1993) Hellinga & Evans, Eur. J. Biochem. 149: 363-373 (1985) Hsiao et al., J. Mol. Biol. 262: 225-242 (1996) Jacobson & Quiocho, J. Mol. Biol. 204: 783-787 (1988) Joshi & Ames, GenBank Accession Number U47027 (1996) Ledvina et al., Proc. Natl. Acad. Sci. USA 93: 6786-6791 (1996) Luecke & Quiocho, Nature 347: 402-406 (1990) Magota et al., J. Bacteriol. 157: 909-917 (1984) Medveczky & Rosenberg, Biochim. Biophys. Acta 192: 369-371 (1969) Miller et al., J. Biol. Chem. 258: 13665-13672 (1983) Mowbray & Cole, J. Mol. Biol. 225: 155-175 (1992) Nickitenko et al., Biochemistry 34: 16585-16595 (1995) Nohno et al., Molec. Gen. Genet. 205: 260-269 (1986) Pflugrath & Quiocho, Nature 314: 257-260 (1985) Quiocho et al., Structure 5: 997-1015 (1997) Quiocho & Vyas, Nature 310: 381-386 (1984) Sanders et al., Infect. Immun. 62: 4515-4525 (1994) Scholle et al., Molec. Gen. Genet. 208; 247-253 (1987) Scripture et al., J. Mol. Biol. 197: 37-46 (1987) Schwartz et al., Eur. J. Biochem. 71; 167-170 (1976) Sharff et al Biochemistry 31: 10657-10663 (1992) Smith et al., Microbiology 145: 2891-2901 (1999) Spurlino et al., J. Biol. Chem. 266: 5202-5219 (1991) Sun et al., J. Mol. Biol. 278: 219-229 (1998) Vyas et al., Biochemistry 33: 4762-4768 (1994) Vyas et al., Science 242: 1290-1295 (1988) Weiner et al., Arch. Biochem. Biophys. 142: 715-717 (1971) Willis & Furlong, J. Biol. Chem. 249: 6926-6929 (1974) Willis & Furlong, J. Biol. Chem. 250: 2574-2580 (1975) Yao et al., Biochemistry 33: 4769-4779 (1994)

Various types of samples may be used in methods provided herein. In non-limiting examples, a sample may comprise a reaction product, a buffer, and/or a solvent. In some embodiments, the solvent is an aqueous solvent. In some embodiments, the solvent comprises a non-polar solvent, a polar aprotic solvent, and/or a polar protic solvent. For example, a sample may comprise water, liquid ammonia, liquid sulfur dioxide, sulfuryl chloride, sulfuryl chloride fluoride, phosphoryl chloride, dinitrogen tetroxide, antimony trichloride, bromine pentafluoride, hydrogen fluoride, dimethyl sulfoxide, hexane, benzene, toluene, 1,4-dioxane, chlorogorm, diethyl ether, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, acetonitrile, tormic acid, n-butanol, isopropanol, nitromethane, ethanol, methanol, and/or acetic acid.

In embodiments, a sample comprises a Newtonian liquid, a shear thickening liquid, a shear thinning liquid, a thixotropic liquid, a rheopectic liquid, or a Bingham plastic. In some implementations, a sample has a dynamic viscosity of at least about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, or 2 pascal-seconds (Pa·s) or less than about 2, 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, 0.5 Pa·s; and/or a kinematic viscosity of at least about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, or 2 centistokes (cSt) or less than about 2, 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, 0.5 cSt.

In various embodiments, the sample comprises a biological sample. The sample may comprise, e.g., a clinical sample (i.e., a sample collected in a clinical or veterinary setting, e.g., by or at the request or supervision or direction of a doctor, nurse, aid worker, or medic) and/or a physiological sample (a sample collected from an organism, e.g., a mammal such as a human) In certain embodiments, the biological sample comprises or has been provided or obtained from a skin surface or a mucosal surface. In some embodiments, the biological sample comprises a biological fluid. Non-limiting examples of biological fluids include sweat, tear fluid, blood, serum, plasma, interstitial fluid, amniotic fluid, sputum, gastric lavage, skin oil, milk, fecal matter, emesis, bile, saliva, urine, mucous, semen, lymph, spinal fluid, synovial fluid, a cell lysate, venom, hemolymph, and fluid obtained from plants such as the fluid transported in xylem cells or phloem sieve tube elements of a plant (e.g. sap).

The present subject matter also provides biosensors, methods, compositions, and devices useful for measuring the level of a ligand within a liquid solution or suspension or composition comprising cultured cells or tissue or a supernatant of such a solution or suspension, e.g., a sample of conditioned media or a sample of growth media in which a polulation of cells was cultured. In some embodiments, the sample is within a culture (e.g., inserted into a bioreactor) or provided from a media, culture, or reaction, e.g., in a bioreactor. For example, the sample may be within or provided from a fermenter such as a culture or culture supernatant from a fermentation reaction (e.g., an ongoing fermentation). Thus, the level of a ligand can be assayed at a timepoint of interest or at a series of timepoints over the duration of cell culture, e.g. continuously, in or from a reaction or culture. Bioreactors include devices or systems that support a biologically active environment. For example, a bioreactor may comprise a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. Such a process can either be aerobic or anaerobic. Organisms growing in bioreactors may be, e.g., submerged or suspended in liquid medium or may be attached to the surface of a solid medium. Submerged cultures may be suspended or immobilized. Suspension bioreactors can use a wider variety of organisms, since special attachment surfaces are not needed, and can operate at much larger scale than immobilized cultures. However, in a continuously operated process the organisms will be removed from the reactor with the effluent Immobilization is a general term describing a wide variety of cell or particle attachment or entrapment. It can be applied to basically all types of biocatalysis including enzymes, cellular organelles, and cells (e.g., animal cells, plant cells, fungal cells, and bacterial cells) Immobilization is useful for continuously operated processes, since the organisms will not be removed with the reactor effluent, but is limited in scale because the cells are only present on the surfaces of the vessel. A bioreactor may also refer to a device or system meant to grow cells or tissues in the context of cell culture. The interogation and/or monitoring of glucose levels in such samples permits the evaluation of the status of growth of the cells or production of secreted products by the cells to inform harvest or feeding or other modification of the culture.

Aspects of the present subject matter relate to the use of methods and biosensors provided herein to detect contamination.

In some embodiments, the sample comprises an environmental sample. Depending on context, there are instances in which a biological sample may also be, or may be within, an environmental sample. In certain embodiments, an environmental sample comprises a solute obtained from a biological composition, such as bone, nail, hair, shell, or cartilage. In various embodiments, an environmental sample comprises a solute obtained from an environmental substance and/or an environmental surface. For example, the solute may be dissolved/obtained from the environmental substance and/or an environmental surface using an aqueous or nonaqueous solution. In some embodiments, an aqueous may optionally comprise a nonaqueous solvent (e.g., mixed with an aqueous solvent). Non-limiting examples of environmental substances include rock, soil, clay, sand, meteorites, asteroids, dust, plastic, metal, mineral, fossils, sediment, and wood. Non-limiting examples of environmental surfaces include the surface of a vehicle such as a civilian vehicle (e.g., a satellite, a bike, a rocket, an automobile, a truck, a motorcycle, a yacht, a bus, or a plane) or a military vehicle (e.g., a tank, an armored personell carrier, a transport truck, a jeep, a mobile artillery unit, a mobile antiaircraft unit, a minesweeper, a Mine-Resistant Ambush Protected (MRAP) vehicle, a lightweight tactical all-terrain vehicle, a high mobility multipurpose wheeled vehicle, a mobile multiple rocket launch system, an amphibious landing vehicle, a ship, a hovercraft, a submarine, a transport plane, a fighterjet, a helicopter, a rocket, or an Unmanned Arial Vehicle), a drone, a robot, a building, furniture, or an organism other than a human. In some embodiments, the sample comprises an environmental fluid. Non-limiting examples of environmental fluids include marine water, well water, drinking well water, water at the bottom of well dug for petroleum extraction or exploration, melted ice water, pond water, aquarium water, pool water, lake water, mud, stream water, river water, brook water, waste water, treated waste water, reservoir water, rain water, and ground water. In some embodiments, waste water comprises sewage water, septic tank water, agricultural runoff, water from an area in which chemical or oil spill has or is suspected of having occurred (e.g., an oil spill into a marine environment), water from an area where a radiation leak has or is suspected of having occurred (e.g., coolant from a nuclear reactor), water within the plumbing of a building, water within or exiting a research facility, and/or water within or exiting a manufacturing facility such as a factory.

In certain embodiments, the sample comprises a food or beverage additive and/or a food or beverage composition. In some embodiments, the food or beverage composition comprises a fermented composition. In various embodiments, the sample comprises a fluid obtained from a food composition. Alternatively or in addition, the sample may comprise a solute dissolved from a food composition. In some examples, a solute is or has been dissolved from a food composition with an aqueous or nonaqueous solution. In various implementations, an aqueous solution may optionally comprise a nonaqueous solvent. In certain embodiments, a sample comprises a food composition in semisolid or liquid form. Non-limiting examples of such compositions include yogurt, soup, ice cream, a broth, a puree, a shake, a smoothie, a batter, a condiment, a sauce, and any combination thereof. In some implementations, a sample is a food engineering process (e.g., obtained from a food design, storage, transport, or production process or from equipment intended to process, transport, or store food). A food composition may comprise, e.g., a plant or a composition isolated from a plant, and/or an animal or a composition isolated from an animal. In various embodiments, a sample comprises a beverage composition. Non-limiting examples of beverage compositions include soft drinks, fountain beverages, water, coffee, tea, milk, dairy-based beverages, soy-based beverages (e.g., soy milk), almond-based beverages (e.g., almond milk), vegetable juice, fruit juice, fruit juice-flavored drinks, energy drinks, sports and fitness drinks, alcoholic products, and beverages comprising any combination thereof. Non-limiting examples of beverage compositions comprising water include purified water (e.g., filtered water, distilled water, or water purified by reverse osmosis), flavored water, mineral water, spring water, sparkling water, tonic water, and any combination thereof. In various embodiments, the sample comprises alcohol. Non-limiting examples of such samples include samples comprising or obtained/provided from beer, malt beverages, liqueur, wine, spirits, and any combination thereof.

In some embodiments, a sample comprises a nutritional or supplement composition. In certain implementations, the nutritional or supplement composition comprises an omega-3 fatty acid, a vitamin, a mineral, a protein powder, or a meal supplement.

In certain embodiments, a biosensor is implanted in a subject's body. For example, a biosensor may be implanted in a subject's blood vessel, vein, eye, natural or artificial pancreas, alimentary canal, stomach, intestine, esophagus, or skin (e.g., within the skin or under the skin). In various embodiments, the biosensor is configured within or on the surface of a contact lens. In some embodiments, the biosensor is configured to be implanted in or under the skin. In non-limiting examples, the biosensor is implanted in a subject with an optode and/or a microbead. In certain embodiments, the biosensor generates a signal transdermally.

Aspects of the present subject matter provide a method for assaying the level of glucose in a subject. The method may comprise contacting a biological sample from the subject with a biosensor for glucose under conditions such that the biosensor binds to glucose present in the biological sample. The biosensor comprises a glucose-galactose binding protein attached to a reporter group, and binding of glucose to a glucose-binding domain of the glucose-galactose binding protein causes a change in signaling by the reporter group. In various embodiments, the subject has or is suspected of having diabetes, such as Type I diabetes or Type II diabetes. In some embodiments, the biological sample comprises blood, plasma, serum, sweat, tear fluid, or urine. In certain embodiments, the biological sample is present in or on the surface of said subject. In various implementations, the biosensor is applied onto or inserted into the subject. For example, the biosensor may be tattooed into the subject or is in or on a device that is implanted into said subject. In some embodiments, the biosensor may be present in or on a contact lens that is worn by the subject. Methods for determining the level of glucose, e.g. in a subject who has or is suspected of having diabetes, may be performed without other testing related to diabetes performed as part of a battery of clinical testing.

The present subject matter includes a method for monitoring the level of a ligand, comprising periodically or continuously detecting the level of the ligand, wherein detecting the level of the ligand comprises (a) providing or obtaining a sample; (b) contacting said sample with a biosensor for said ligand according to claim 1 under conditions such that the ligand-binding protein of said biosensor binds to said ligand, and (c) detecting a signal produced by said biosensor.

Aspects of the present subject matter also provide a method for monitoring the level of a ligand (e.g., glucose and/or galactose) in a subject, comprising periodically detecting the level of the ligand in the subject. Detecting the level of the ligand in the subject may comprise (a) providing or obtaining a biological sample from said subject; (b) contacting the biological sample with a biosensor for the ligand provided herein under conditions such that the ligand-binding protein of the biosensor binds to the ligand, if the ligand is present in said biological sample, and (c) detecting (i) a signal produced by a reporter group of said biosensor, or (ii) whether a signal is produced by a reporter group of said biosensor. The level of said ligand may be detected, e.g., at least once every 1, 2, 3, 6, or 12 hours, at least once every 1, 2, 3, or 4 days, at least once every 1, 2, or three weeks, or at least once every 1, 2, 3, 4, 6, or 12 months.

The present subject matter also provides a method for monitoring the level of a ligand in a subject. The method comprises (a) administering a biosensor provided herein or a device comprising a biosensor provided herein to said subject, wherein after administration the biosensor is in contact with a bodily fluid or surface that typically comprises said ligand, and (b) detecting (i) a signal produced by a reporter group of the biosensor continuously or repeatedly at intervals less than about 30 minutes (m), 15 m, 10 m, 5 m, 1 m, 30 seconds (s), 15 s, 10 s, 5 s, 1 s, 0.1 s, 0.001 s, 0.0001 s, or 0.00001 apart, and/or (ii) whether a signal is produced by a reporter group of the biosensor continuously or repeatedly at intervals less than about 30 m, 15 m, 10 m, 5 m, 1 m, 30 s, 15 s, 10 s, 5 s, 1 s, 0.1 s, 0.001 s, 0.0001 s, or 0.00001 apart.

Non-limiting aspects of continuously monitoring glucose levels are described in Weidemaier et al. (2011) Biosensors and Bioelectronics 26, 4117-4123 and Judge et al. (2011) Diabetes Technology & Therapeutics, 13(3):309-317, the entire contents of each of which are hereby incorporated herein by reference.

Also within the invention is a composition comprising a purified thermostable, glucose-binding fluorescently-responsive sensor protein and a solid substrate, e.g., a particle, a bead such as a magnetic bead, or a planar surface such as a chip or slide, wherein the sensor protein is immobilized onto the solid substrate. An exemplary solid substrate solid substrate comprises a cyclic olefin copolymer.

The sensor protein contains a single cysteine residue, with the single cysteine residue being located in a glucose-contacting site of protein. A thermostable glucose sensor protein is one in which the activity (glucose binding) is unaffected by relatively high temperatures. For example, the glucose sensor protein comprises a mid-point thermal melt transition greater than 50° C., greater than 60° C., greater than 70° C., greater than 80° C., greater than 90° C., or greater than 100° C. In some examples, the protein comprises the amino acid sequence of SEQ ID NO: 298, and in some examples, the single cysteine is conjugated to Badan, Acrylodan, or a derivative thereof. For example, the derivative comprises a replacement of the two-ring naphthalene of Acrylodan or Badan with a three-ring anthracene, a fluorene, or a styrene. A reporter group is covalently bound to the single cysteine. In some situations, the solid substrate comprises a plurality of sensor proteins, each of which comprises a different dissociation constant (K_(D)) for glucose, e.g., for detecting and quantifying glucose levels across many ranges of concentrations.

The invention also includes a composition comprising purified glucose sensor protein with less than 65% identity and greater than 27% identity (e.g., 44-48% sequence identity) to SEQ ID NO: 1, 16, or 17, wherein the sensor protein comprises a single cysteine residue, said residue being located in a glucose-contacting site of the protein, and a solid substrate, such that the sensor protein is immobilized onto said solid substrate. As described above, a reporter group is covalently bound to the single cysteine. In some example, the solid substrate comprises a plurality of sensor proteins, each of which comprises a different dissociation constant (K_(D)) for glucose for sensing over a wide range or ranges of glucose concentrations.

A method of detecting the presence of or the quantity of glucose in a test sample is carried out using the following steps: contacting the testsample with the biosensor or sensor protein/solid support construct to yield a complex of glucose and the ligand-binding protein or biosensor protein; contacting the complex with an excitation light; measuring an emission intensity of the reporter group from at least two wavelengths; computing a ratiometric signal from the two (or more) wavelengths; and comparing the signal to a known glucose binding curve of signals to identify the presence of or calculate the quantity of glucose in the test sample. The test sample may be obtained from a variety of sources. For example, the test sample is selected from a bodily fluid, a food, a beverage, or a bioreactor culture broth. The testing method may be carried out in vivo, e.g., using an implantable device or dermal patch, or ex vivo.

In various embodiments, the subject to be tested is a mammal, e.g., a primate (such as a human, a monkey, a chimpanzee, or a gorilla), a fish, a bird, a reptile, an amphibian, or an arthropod. In some embodiments, the subject is a fish, a cow, a pig, a camel, a llama, a horse, a race horse, a work horse, a goat, a rabbit, a sheep, a hamster, a guinea pig, a cat, a wolf, a dog (e.g., a pet dog, a work dog, a police dog, or a military dog), a rat, a mouse, a seal, a whale, a manatee, a lizard, a snake, a chicken, a goose, a swan, a duck, or a penguin.

Exemplary Devices and Compositions Comprising Biosensors

Aspects of the present subject matter provide a device comprising one or more biosensors provided herein. Such devices may be, e.g., wearable, implantable, portable, or fixed.

In some embodiments, the device is a nanoparticle or a microparticle comprising said biosensor. Non-limiting examples of devices include devices comprising a test strip, patch, plate, bead, or chip comprising a biosensor provided herein. In certain embodiments, a device may comprise a desiccated biosensor.

The present subject matter also provides a contact lens or a skin patch comprising a biosensor provided herein. In some embodiments, the biosensor is throughout the contact lens or skin patch or within a particular region or zone of a contact lens or skin patch (e.g., in one or more shapes (e.g., a square, circle, or star), dots, lines, or zones, located at the periphery or a portion of the periphery of a contact lens or patch). In some embodiments, the skin patch comprises an adhesive that facilitates attachment of the patch to the surface of skin.

Devices provided herein may include a variety of structural compositions. For example, many polymers (including copolymers), and plastics may be used. Non-limiting examples of compositions useful in certain devices include glass, polystyrene, polypropylene, cyclic olefin copolymers, ethylene-norbornene copolymers, polyethylene, dextran, nylon, amylase, paper, a natural cellulose, a modified cellulose, a polyacrylamide, gabbros, gold, and magnetite (as well as combinations thereof). In some embodiments, the device comprises a hydrogel, a cryogel, or a soluble gel. For example, the biosensor may be incorporated into or onto the hydrogel, cryogel, or soluble gel. In various embodiments, the device comprises a matrix comprising nanopores, micropores, and/or macropores. In certain embodiments, the surface of a device comprises a polymer. In an embodiment, the surface comprises the surface of a particle or a bead having a diameter of about 0.001-1, 0.001-0.1, 0.01-0.1, 0.001-0.01, 0.1-1, 0.1-0.5, or 0.01-0.5 centimeters (cm). For example, the particle comprises a nanoparticle or a microparticle.

Non-limiting examples of polymers include cyclic olefin copolymers, ethylene-norbornene copolymers, polylactic acid, polyglycolic acid, agarose, alginate, poly(lactide-co-glycolide), gelatin, collagen, agarose, natural and synthetic polysaccharides, polyamino acids, poly(lysine), polyesters, polyhydroxybutyrates, polyanhydrides, polyphosphazines, polyvinyl alcohol, polyalkylene oxide, polyethylene oxide, polyallylamines, polyacrylates, modified styrene polymers, poly(4-aminomethylstyrene), pluronic polyols, polyoxamers, polyuronic acid, and polyvinylpyrrolidone.

In some embodiments, the device comprises a plastic polymer comprising cyclic olefin copolymer (COC), such as e.g. TOPAS® COC. Several types of cyclic olefin copolymers are available based on different types of cyclic monomers and polymerization methods. Cyclic olefin copolymers are produced by chain copolymerization of cyclic monomers such as 8,9,10-trinorborn-2-ene (norbornene) or 1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene (tetracyclododecene) with ethene (such as TOPAS Advanced Polymer's TOPAS, Mitsui Chemical's APEL), or by ring-opening metathesis polymerization of various cyclic monomers followed by hydrogenation (Japan Synthetic Rubber's ARTON, Zeon Chemical's Zeonex and Zeonor). See, e.g., International Union of Pure and Applied Chemistry (2005) Purr. Appl. Chem. 77(5):801-814. These later materials using a single type of monomer may be referred to as cyclic olefin polymers (COPs). A CAS Registry number for COC is 26007-43-2.

In certain embodiments, the device is attached to a surface of a device or is not attached to a surface of said device (e.g., the biosensor is present loosely within the device as a component of a solution or powder).

A biosensor may be attached to a device via a variety or means, e.g., via attachment motif. In some embodiments, the attachment motif is attached to the N-terminus or the C-terminus of the biosensor. In certain embodiments, the biosensor is linked to an attachment motif via a covalent bond. In various embodiments, the biosensor is linked to said attachment motif via a linker. A non-limiting example of a linker is a polyglycine comprising 2, 3, 4, 5, or more glycines and optionally further comprising a serine. In some embodiments, the attachment motif comprises a polypeptide. Non-limiting examples of polypeptides useful in attachment moieties include hexahistidine peptides, hexalysine peptides, zinc-finger domains (ZF-QNKs), and disulfide-containing truncated zinc fingers (βZifs). An example of a hexalysine peptide comprises amino acids in the sequence of SEQ ID NO: 296, an example of a ZF-QNK comprises amino acids in the sequence of SEQ ID NO: 294, and an example of a βZif comprises amino acids in the sequence of SEQ ID NO: 293. In some embodiments, the attachment motif comprises a polypeptide that binds to plastic or cellulose.

The hexahistidine, hexalysine, βZif and QNK-ZF fusions (SEQ ID NOS: 173 and 175-181) enable FRSs to be immobilized onto chemically functionalized surfaces. Non-limiting aspects of chemically functionalized surfaces are discussed in Biju, V. (2014) Chem Soc Rev, 43, 744-64 and McDonagh (2008) Chem Rev, 108, 400-422, the entire contents of which are incorporated herein by reference. Directed evolution methods have been used to develop peptides that bind directly to non-functionalized surfaces (Care, Bergquist and Sunna 2015 Trends Biotechnol, 33, 259-68; Baneyx 2007 Curr. Opin. Biotechnol., 18, 312-317; Gunay and Klok 2015 Bioconjug Chem, 26, 2002-15), including various plastics (Adey et al. 1995 Gene, 156, 27-31; Serizawa et al. 2005 J Am Chem Soc, 127, 13780-1; Serizawa, Sawada and Kitayama 2007a Angew Chem Int Ed Engl, 46, 723-6; Serizawa, Sawada and Matsuno 2007b Langmuir, 23, 11127-33; Serizawa, Techawanitchai and Matsuno 2007c Chembiochem, 8, 989-93; Matsuno et al. 2008 Langmuir, 24, 6399-403; Chen, Serizawa and Komiyama 2011 J Pept Sci, 17, 163-8; Kumada 2010 J. Biosci. and BioEng., 109, 583-587; Date et al. 2011 ACS Appl Mater Interfaces, 3, 351-9; Kumada 2012, Vodnik, Strukelj and Lunder 2012 J. Biotech., 160, 222-228; Kumada 2014 Biochem. et Biophys. Acta, 1844, 1960-1969; Ejima, Matsuno and Serizawa 2010 Langmuir, 26, 17278-85), inorganic materials(Hnilova 2012 Soft Matter, 8, 4327-4334; Care et al. 2015 Trends Biotechnol, 33, 259-68), nanoparticles (Avvakumova et al. 2014 Trends Biotechnol, 32, 11-20), and cellulosic paper (Guo et al. 2013 Biomacromolecules, 14, 1795-805). Such peptides, or natural material-binding domains (Oliveira et al. 2015 Biotechnol Adv, 33, 358-69), also can be fused to FRSs to direct site-specific, oriented immobilization on their target materials while preserving FRS function. For instance, plastic-binding peptides have been developed that direct immobilization on polystyrene (Adey et al. 1995 Gene, 156, 27-31; Serizawa et al. 2007c Chembiochem, 8, 989-93; Kumada 2010 Biochem. et Biophys. Acta, 1844, 1960-1969; Vodnik et al. 2012 Anal Biochem, 424, 83-6), polymethyl acrylate (Serizawa et al. 2005 J Am Chem Soc, 127, 13780-1; Serizawa et al. 2007a Angew Chem Int Ed Engl, 46, 723-6; Serizawa et al. 2007b Langmuir, 23, 11127-33; Kumada 2014 Biochem. et Biophys. Acta, 1844, 1960-1969), polycarbonate (Kumada 2012 J. Biotech., 160, 222-228), polylactide (Matsuno et al. 2008 Langmuir, 24, 6399-403), and polyphenylene vinylene (Ejima et al. 2010 Langmuir, 26, 17278-85). Cellulose-binding peptides (Guo et al. 2013 Biomacromolecules, 14, 1795-805) and natural domains (Oliveira et al. 2015 Biotechnol Adv, 33, 358-69; Shoseyov, Shani and Levy 2006 Microbiol Mol Biol Rev, 70, 283-95) can be used to immobilize fusion proteins on paper. Inorganic material include noble metals (Hnilova 2012 Soft Matter, 8, 4327-4334), semi-conductors (Care et al. 2015 Trends Biotechnol, 33, 259-68), and fluorescent quantum dots(Medintz et al. 2005 Nat Mater, 4, 435-46; Lee et al. 2002 Science, 296, 892-5). The entire contents of each of the references above (and all other references herein) is incorporated herein by reference.

In some embodiments, the attachment motif is attached to a device surface and/or within a matrix of the device. In some embodiments, a biosensor is attached to an attachment motif via a covalent bond and the attachment motif is attached to a device via a covalent bond. Non-limiting examples of covalent bonds include disulfide bonds, ester bonds, thioester bonds, amide bonds, and bonds that have been formed by click reactions. Non-limiting examples of a click reaction include a reaction between an azide and an alkyne; an azide and an alkyne in the presence of Cu(I); an azide and a strained cyclooctyne; an azide and a dibenzylcyclooctyne, a difluorooctyne, or a biarylazacyclooctynone; a diaryl-strained-cyclooctyne and a 1,3-nitron; an azide, a tetrazine, or a tetrazole and a strained alkene; an azide, a tetrazine, or a tretrazole and a oxanorbornadiene, a cyclooctene, or a trans-cycloalkene; a tetrazole and an alkene; or a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene.

Alternatively or in addition, a surface of a device may be modified to contain a moiety (e.g. a reactive group) what facilitates the attachment of a biosensor and/or binds to the biosensor. In some embodiments, the biosensor is attached to a surface via a biotin-avidin interaction.

In various implementations, the device comprises a first region for receiving a sample and second a region that comprises the biosensor, wherein said first region is separated from said second region by a filter. In some examples, the filter is impermeable to compounds greater than about 1, 2, 3, 4, 5, 10, 50, 200, or 250 kiloDalton (kDa) in size. The sample may comprise, e.g., a tube, such as a tube that is configured for centrifugation. When sample is placed into the first region and the device is centrifuged, then a portion of the sample comprising a ligand flows through the filter into the second region where the biosensor is contacted.

Non-limiting examples of devices provided herein include endoscopy probes and colonoscopy probes.

In some embodiments, the device comprises an optode. In non-limiting examples, the optode comprises an optical fiber and a single biosensor or composite biosensor. In certain embodiments, the single biosensor or composite biosensor is immobilized on the surface or at an end of the optical fiber. In some embodiments, the optode is configured for implantation into a subject. Alternatively or in addition, the optode is configured for insertion into a sample.

The devices provided herein may optionally comprise a biosensor panel, a composite sensor, a sensor array, and/or a composition comprising a plurality of biosensors. In various embodiments, a device comprises multiple glucose and/or galactose biosensors that detect a range of different glucose and/or galactose concentrations in a single sample and/or assay run (i.e., each biosensor has a different affinity for glucose and/or galactose). Devices may provide spatial localization of multiple biosensors to provide the necessary addressability of different elements in a multi-sensor array comprising sensors that differ in their engineered affinities for coverage of a wide range of glucose concentrations, or sensors that each detects distinct analytes.

Aspects of the present subject matter provide a biosensor panel comprising a plurality of biosensors, wherein said plurality of biosensors comprises at least one biosensor disclosed herein. In some embodiments, the plurality comprises at least about 2, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 biosensors.

The present subject matter also provides a composite sensor. The composite sensor may comprise a sensor element, wherein the sensor element comprises 2 or more biosensors, wherein at least 1 of said 2 or more biosensors is a biosensor disclosed herein. In some embodiments, the biosensors are not spatially separated in the sensor element, e.g., the biosensors are mixed within a solution or on a surface of the sensor element. In various embodiments, the composite sensor comprises a plurality of sensor elements, wherein each sensor element of the plurality of sensor elements comprises 2 or more biosensors, wherein at least 1 of the 2 or more biosensors is a biosensor provided herein. In some embodiments, the plurality of sensor elements comprises at least about 2, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 sensor elements.

Also included herein is a sensor array comprising a plurality of biosensors of the present subject matter. The sensor array may include, e.g., multichannel array or a multiplexed array. In some embodiments, the biosensors of the plurality of biosensors are spatially separated from each other. In certain embodiments, the biosensors are arranged linearly or in a grid on a surface of said array.

The present subject matter provides a composition comprising a plurality of biosensors including at least one biosensor disclosed herein. Also provided is a non-human mammal comprising a biosensor or device disclosed herein.

Exemplary Polypeptides and Polynucleotides

The present subject matter provides polynucleotides encoding any one of the polypeptides disclosed herein. The polypeptides are also provided. In various embodiments, the polynucleotides are codon-optimized for expression in a desired host cell, such as bacterial cells (e.g., E. coli), yeast, insect cells, plant cells, algal cells, or mammalian cells. The polypeptides provided herein include polypeptides comprising the amino acid sequence of any one of SEQ ID NOS: 1-103, 157-292, 197, or 198. The polynucleotides provided herein include polynucleotides encoding a polypeptide comprising the amino acid sequence of any one of SEQ ID NOS: 1-103, 157-292, 197, or 198.

The polypeptides and biosensors provided herein may be in a variety of forms, e.g., purified in solution, dried (e.g. lyophilized) such as in the form of a powder, and in the form of a crystal (e.g., a crystal suitable for x-ray crystallography). Thus, aspects of the present subject matter provide crystal structures and crystalized forms of the ligand-binding proteins and biosensors disclosed herein. Such crystal structures and crystalized proteins are useful for designing and optimizing biosensors using principles and methods discussed herein.

Also provided are expression vectors comprising a polynucleotide of the present subject matter and/or encoding a polypeptide disclosed herein. Non-limiting examples of expression vectors include viral vectors and plasmid vectors. In some embodiments, an expression vector comprises nucleotides in the sequence set forth as SEQ ID NO: 105-156. In various embodiments, a polynucleotide encoding a ligand-binding protein and/or biosensor is operably linked to a promoter. The promoter may be expressed, e.g., in a prokaryotic and/or a eukaryotic cell.

The subject matter further includes an isolated cell comprising an expression vector provided herein. The isolated cell may be, e.g., a bacterial cell, a yeast cell, an algal cell, a plant cell, an insect cell, or a mammalian cell. Also included is a non-human multicellular organism such as a plant or an animal (e.g., an insect, a mammal, a worm, a fish, a bird, or a reptile) comprising an expression vector disclosed herein.

Exemplary Methods for Designing Biosensors

Aspects of the present subject matter provide method of identifying a candidate ligand-binding protein for use in a biosensor, comprising: (a) selecting a first protein having a known amino acid sequence (seed sequence), wherein the first protein is a glucose-galactose binding protein; (b) identifying a second protein having an amino acid sequence (hit sequence) with at least 15% sequence identity to the seed sequence; (c) aligning the seed amino acid sequence and the hit sequence, and comparing the hit sequence with the seed sequence at positions of the seed sequence that correspond to at least 5 primary complementary surface (PCS) amino acids, wherein each of the at least 5 PCS amino acids has a hydrogen bond interaction or a van der Waals interaction with glucose when glucose is bound to the first protein; and (d) identifying the second protein to be a candidate ligand-binding protein if the hit sequence comprises at least 5 amino acids that are consistent with the PCS.

The present subject matter also includes a method for constructing a candidate biosensor, comprising: (a) providing a candidate ligand-binding protein; (b) generating a structure of the second protein; (c) identifying at least one putative allosteric, endosteric, or peristeric site of the second protein based on the structure; (d) mutating the second protein to substitute an amino acid at said at least one putative allosteric, endosteric, or peristeric site of the second protein with a cysteine; and (e) conjugating a fluorescent compound to the cysteine. In some embodiments, the structure comprises a homology model of the second protein generated using a structure of the first protein. In some embodiments, the structure comprises a structure experimentally determined by nuclear magnetic resonance spectroscopy or X-ray crystallography.

Aspects of the present subject matter further provide a method for constructing a biosensor comprising a desired dissociation constant (KD) for glucose, comprising: (a) providing an initial biosensor that does not comprise the desired KD for glucose, wherein said initial biosensor is a biosensor provided herein; (b) mutating the initial biosensor to (i) alter a direct interaction in the PCS between the initial biosensor and bound glucose; (ii) manipulate the equilibrium between open and closed states of the initial biosensor; (iii) alter an interaction between the ligand-binding protein and the reporter group of the initial biosensor; or (iv) alter an indirect interaction that alters the geometry of the binding site of the biosensor, to produce a modified biosensor; and (c) selecting the modified biosensor if the modified biosensor comprises the desired KD for glucose. In some embodiments, the reporter comprises Acrylodan, Badan, or a derivative thereof, and mutating the initial biosensor in (b) comprises altering an interaction between the ligand-binding protein and a carbonyl group of the Acrylodan, Badan, or derivative thereof. In some embodiments, the reporter group comprises Acrylodan, Badan, or a derivative thereof, and mutating the initial biosensor in (b) comprises altering an interaction between the ligand-binding protein and a naphthalene ring of the Acrylodan, Badan, or derivative thereof. In some embodiments, mutating the initial biosensor comprises introducing a substitution mutation into said initial biosensor. In some embodiments, the method further comprises immobilizing said affinity-tuned biosensor on a substrate.

In some embodiments, the second protein comprises (i) amino acids in the sequence of SEQ ID NO: 1-15 or 17-31; (ii) a stretch of amino acids in a sequence that is least about 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 1-31; (iii) a stretch of at least about 50, 100, 150, 200, 250, 300, or 350 amino acids in a sequence that is at least about 95, 96, 97, 98, or 99% identical to a sequence within SEQ ID NO: 1-31; or (iv) a stretch of at least about 50, 100, 150, 200, 250, 300, or 350 amino acids in a sequence that is identical to a sequence within SEQ ID NO: 1-31. In various embodiments, attaching the reporter group to the putative allosteric, endosteric, or peristeric site of the first protein comprises substituting a cysteine at the site with a cysteine. For example, the reporter group is conjugated to the cysteine. Preferably, attaching a reporter group to the corresponding amino acid of the second protein produces a functional biosensor.

The selected first protein (e.g., the amino acid sequence thereof) may be novel or known. However, in many instances, the function of the first protein will not be known. In a non-limiting example, identifying a protein not previously known to have glucose binding activity may comprise a structurally assisted functional evaluation (SAFE) homolog search method comprising the following steps:

(1) Collecting a sequence homology set using a BLAST sequence alignment tool starting with glucose-galactose binding protein (GGBP) sequence disclosed herein as a seed. Permissive settings are used, such that pairwise hits are required to have a minimum of only, e.g., 20%, 25%, 30%, 35% or 40% sequence identity with the seed sequence. The lengths of the hit and seed are mutually constrained such that the alignment covers at least, e.g., 60%, 65%, 70%, 85%, or 90% within each partner.

(2) Structure-based encoding of biological function: A primary complementary surface (PCS) comprising the protein residues that form hydrogen bonds and van der Waals contacts with a bound glucose is defined using computer-assisted, visual inspection of the three-dimensional structure of the GGBP-glucose complex. This definition specifies residue positions and their permitted amino acid identity. Multiple amino acid identities are permitted at each position to encode functionally equivalent residues. This definition establishes a search filter for the accurate prediction of glucose-binding proteins within the universe of sequence homologs collected in (1). For example, a candidate's residue corresponding to position 14 of ecGGBP may be D or N, a candidate's residue corresponding to position 16 of ecGGBP may be F, Y, or W, a candidate's residue corresponding to position 91 of ecGGBP may be N or D, a candidate's residue corresponding to position 152 of ecGGBP may be H, N, or Q, a candidate's residue corresponding to position 154 of ecGGBP may be D or N, a candidate's residue corresponding to position 158 of ecGGBP may be R, a candidate's residue corresponding to position 183 of ecGGBP may be W, F, or Y, a candidate's residue corresponding to position 211 of ecGGBP may be N or D, a candidate's residue corresponding to position 236 of ecGGBP may be D or N, and a candidate's residue corresponding to position 256 of ecGGBP may be N or D.

(3) Accurate sequence alignment: Tools such as ClustalW are used to construct an accurate alignment of all the sequence homologs. The GGBP seed sequence is included in the alignment. This multiple sequence alignment establishes the equivalent positions of the seed GGBP (primary complementary surface) PCS in each sequence homolog.

(4) Function evaluation: The glucose-binding properties of each of the aligned sequence homologs is determined by measuring their compliance with the PCS sequence filter. A “Hamming distance”, H, is assigned for each homolog, which specifies the degree of sequence identity of all the residues at the aligned PCS positions. A value of H=0 indicates that the identities of all the residues at the aligned PCS positions match the amino acid(s) allowed in the PCS search filter; H>0, indicates that one or more aligned positions have disallowed residues. Sequences for which H=0 are predicted to encode glucose-binding proteins.

(5) Selection of representative SAFE homologs: The sequence homologs are ordered by (a) identity with the seed PCS, as measured by the Hamming distance, (b) fractional overall sequence identity with the seed sequence. A subset for sequences with H=0, sampling the fractional overall sequence identity is selected for experimental verification.

In a non-limiting example, identifying a protein not previously known to have glucose binding activity may comprises the following steps:

(1) performing a computational search of sequence databases to define a broad group of simple sequence or structural homologs of any known, glucose-galactose binding protein;

(2) using the list from step (1), deriving a search profile containing common sequence and/or structural motifs shared by the members of the list [e.g. by using computer programs such as MEME (Multiple Em for Motif Elicitation available at meme.sdsc.edu/meme/cgi-bin/meme.cgi) or BLAST];

(3) searching sequence/structural databases, using a derived search profile based on the common sequence or structural motif from step (2) as query (e.g., using computer programs such as BLAST, or MAST (Motif Alignment Search Tool available at meme.sdsc.edu/meme/cgi-bin/mast.cgi), and identifying a candidate sequence, wherein a sequence homology and/or structural similarity to a reference glucose-galactose binding protein is a predetermined percentage threshold;

(4) compiling a list of candidate sequences to generate a list of candidate glucose-galactose binding proteins;

(5) expressing the candidate glucose-binding proteins in a host organism; and

(6) testing for glucose and/orgalactose binding activity, wherein detection of glucose and/or galactose binding in said organism (or the media thereof) indicates that the candidate sequence comprises a novel glucose and/or galactose binding protein.

In non-limiting examples, the MEME suite of sequence analysis tools (meme.sdsc.edu/meme/cgi-bin/meme.cgi) can also be used as an alternative to BLAST. Sequence motifs are discovered using the program “MEME”. These motifs can then be used to search sequence databases using the program “MAST.” The BLAST search algorithm is well-known.

Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the invention.

Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below.

DESCRIPTION OF THE DRAWINGS

FIGS. 1A-C are a cartoon and graphs illustrating emission spectra changes upon ligand binding to FRSs. (A) FRSs can be constructed by site-specifically attaching a fluorophore to a protein that undergoes a conformational change upon binding ligand (triangle), such that the shape and intensities of the fluorescent conjugate emission spectra changes. (B) In the absence of ligand, the emitted fluorescence color is predominantly blue, whereas the ligand complex fluoresces green. Arrows indicate the direction of change upon ligand addition. (C) Ligand binding is determined by measuring the ratio of blue to green emission intensities.

FIGS. 2A-C are structural illustrations and a table showing exemplary features of the E. coli glucose-galactose binding protein (ecGGBP). (A) The glucose and calcium complex [PDB identifier 2gbp (Vyas et al. 1988)], glucose is sandwiched by van der Waals contacts with the rings of Phe16 and Trp183. (B) Residues that form hydrogen bonds with the bound glucose. The primary complementary surface (PCS) comprises the aromatic sandwich and the hydrogen-bonding residues. (C) The PCS sequence filter used to identify the subset of glucose-binding proteins within a family of sequence ecGGBP homologs. Note redundancies in the allowed residues at each position (the first amino acid listed corresponds to the wild-type ecGGBP sequence).

FIG. 3 is an alignment of the homologs predicted to be glucose-binding proteins (alignment generated by ClustalW; ordered by fractional sequence identity to the ecGGBP seed sequence). Sequences taken from Table 1 (name, line number in Table 1, accession code, species, fractional identity to ecGGBP):

ecGGBP, 2, NC_013654|YP_003350022.1, Escherichia coli, 100%;

ttGGBP, 96, NC_014410|YP_003852930.1, Thermoanearobacterium thermosaccharolyticum, 48%;

cobGGBP, 94, NC_014392|YP_003839461.1, Caldicellosiruptor obsidiansis, 48%;

chyGGBP, 101, NC_014652|YP_003991244.1, Caldicellulosiruptor hydrothermalis, 47%;

pspGGBP, 112, NC_013406|YP_003243743.1, Paenibacillus sp., 44%;

ereGGBP, 123, NC_012781|YP_002936409.1, Eubacterium rectale, 37%;

cauGGBP, 127, NC_022592|CAETHG_2982, Clostridium autoethanogenum, 36%;

erhGGBP, 124, N_015601|YP_004561181.1, Erysipelthrix rhusiopathiae, 36%;

rinGGBP_B, 126, NC_021012|YP_00777811241, Roseburia intestinalis, 36%;

cljGGBP, 128, NC_014328|CLJU_c08950, Clostridium ljunghaldii, 35%;

fprGGBP, 129, NC_021020|YP_007799070.1, Faecalibacterium prausnitzii, 34%;

rinGGBP_A, 132, NC_021012|YP_007778116.1, Roseburia intestinalis, 33%;

bprGGBP, 137, NC_014387|YP_003830205.1, Butyvibrio proteoclasticus, 30%;

csaGGBP, 138, NC_014376|YP_003822565.1, Clostridium saccharolyticum, 29%.

Numbering according to ecGGBP. Light grey: leader peptides; dark grey, primary complementary surface (PCS) residues; —, position of insertions. Positions of the α helices (α_(x)), β sheets (β_(x)), inter-domain hinge segments (h_(x)), and calcium binding site EF hand (EF) observed in the ecGGBP structure are indicated.

FIGS. 4A and 4B are graphs relating to the analysis of glucose binding by ligand-mediated increases in protein thermostability. Protein (un)folding is monitored by binding of SYPRO to the unfolded state as a function of temperature. Fluorescence intensity increases upon binding of SYPRO by the unfolded state. (A) Temperature dependence of fluorescence emission intensity of csaGGBP (see Tables 1 and 2) in the presence of varying amounts of glucose. (B) The mid-point denaturation temperature, T_(m), increases upon addition of glucose, indicative of glucose binding to the folded state of csaGGBP, as predicted

FIG. 5 is a series of graphs showing temperature- and glucose-dependent ratiometric fluorescent landscapes of the Acrylodan conjugates of GGBP homologs. Rows correspond to the E. coli (ecGGBP), T. thermosaccharolyticum (ttGGBP), C. obsidiansis (cobGGBP), and C. hydrothermalis (chyGGBP) glucose-galactose binding proteins site-specifically labeled with Acrylodan at the endosteric cysteine mutation replacing the tryptophan that contacts the glucose pyranose ring (W183 in ecGGPB). Column I: Three-dimensional landscapes representing the ratio of fluorescence emission intensities (Z axis) at 488 nm and 510 nm as a function of temperature and glucose concentration. Indicated are the main equilibrium states: N, native apo-protein; D, denatured protein; S, saturated glucose complex. Subscripts indicate temperature-dependent conformational sub-states (see main text). Dotted lines indicate approximate mid-points (i.e. ΔG=0) for the equilibria of the underlying reactions: black lines ( - - - ), binding; red (-⋅-⋅-), thermal denaturation; purple ( ⋅ ⋅ ⋅), thermal conformational changes. Column II: Examples of isothermal glucose-binding curves, determined at 310 K (37° C.). For each protein, two panels are shown: top, fit to the ratiometric signal (red line, fit to the ratiometric data only; blue line, joint fit to ratiometric and monochromatic emission intensities); bottom, fit to monochromatic emission intensities (red, 488 nm; blue, 510 nm).

FIG. 6A is a structure showing exemplary positions for introducing cysteine mutations to which fluorophores can be covalently coupled for reagentless biosensor construction are indicated: positions 157, 159, and 300, endosteric; positions 11, 16, 42, 67, 92, 111, 148, 181, and 183, peristeric; positions 17, 91, 151, and 182, allosteric. FIG. 6B shows a structure of Acrylodan. FIG. 6C shows a structure of Badan.

FIG. 7A-F is a series of graphs for glucose-dependent emission spectra of Acrylodan and Badan conjugates of Y11C, F17C and W182C mutants of ttGGBP. Corrected spectra (apo-protein, red; saturated glucose, purple; intermediate glucose concentrations, black): left column, Acrylodan; right column, Badan. Insets, fit of the ratiometric signal (equation 1 and 2; 20 nm integration bandwidth): blue circles, experimentally observed ratios; black line, calculated fit (baselines; apo-protein, constant; saturated glucose complex, linear). (A) Y11C⋅Acrylodan (isochromic; λ₁, 458 nm; λ₂, 511 nm; ^(app)K_(d), 0.14 mM); (B) Y11C⋅Badan (hypsochromic; λ₁, 492 nm; λ₂, 528 nm; ^(app)K_(d), 0.28 mM); (C) F17C⋅Acrylodan (hypsochromic; λ₁, 482 nm; λ₂, 545 nm; ^(app)K_(d), 0.08 mM); (D) F17C⋅Badan (hypsochromic; λ₁, 470 nm; λ₂, 542 nm; ^(app)K_(d), 0.18 mM); (E) F182C⋅Acrylodan (bathochromic; λ₁, 475 nm; λ₂, 545 nm; ^(app)K_(d), 2.2 mM); (F) F182C⋅Badan (isochromic; λ_(d), 474 nm; λ₂, 518 nm; ^(app)K_(d), 26 mM).

FIGS. 8A-P are illustrations of fluorophore structures. Naphthalene family: (A) Acrylodan; (B) Badan; (C) IAEDANS. Xanthene family: (D) Fluorescein (5-IAF and 6-IAF); (E) Oregon Green; (F) Alexa 432; (G) Alexa 532; (H) Alexa 546; (I) Texas Red. Coumarin family: (J) Pacific Blue; (K) CPM. Benzoxadiazole family: (L) IANBD. Boradiazaindacine (BODIPY) family: (M) BODIPY 499/508; (N) BODIPY 507/545. Cyanine family: (O) CyS. Miscellaneous: (P) PyMPO.

FIGS. 9A-H are illustrations of structures of ttGGBP conjugates determined by X-ray crystallography. (A) Overview of the ttGGBP F17C⋅Badan conjugate, viewed from the back of the protein looking through the three hinge strands (h₁-h₃). W182 (magenta) forms extensive van der Waals contacts (translucent surface) with the bound glucose (cyan). The F17C mutation removes the wild-type contacts (translucent surface) between the benzene ring and glucose. The Badan conjugate (blue) points out of the glucose-binding site into the solvent. (B) Overview of the ttGGBP182C2.0⋅Acrylodan conjugate (note that the view point is different from (A). The conjugated Acrylodan also points out into solution. (C) Cutaway illustrating the channels surrounding the bound glucose within which Badan, Acrylodan, and the galactoside R-group (Sooriyaarachchi et al. 2009) (dark gray) are placed. The view is down the long axis of ttGGBP, looking at the glucose-binding surface of the N-terminal domain. The C-terminal domain (with Ca²⁺ site) has been cut away (bisecting the hinge). (D) The electronic densities of the Badan fluorophore and bound sugar are well defined (gray lines, 2F_(o)-F_(c) electron density at 1 σ contour levels). (E) Close-up side-view of Badan illustrates that the fluorophore carbonyl is twisted out the of the naphthalene ring plane. (F) End view, looking down the linker towards the exterior of the binding site shows that the carbonyl torsion is ˜28° (gray lines, 2F_(o)-F_(c) electron density at 1 σ contour levels; arrow, cysteine thiol). (G) The same view of the ecGGBP W183C⋅Acrylodan shows that in this fluorophore the carbonyl is co-planar with the naphthalene ring (blue lines, 2F_(o)-F_(c) electron density at 1 σ contour levels; arrow, cysteine thiol). (H) Close-up view of the fit between the fluorophore carbonyl knob into the hole (translucent surface) formed by van der Waals contacts with D238 and N258.

FIGS. 10A and B are structures relating to structure-guided design of affinity mutants. (A) The ttGGBP182C2.0 Acrylodan conjugate structure reveals the presence of a cavity filled with water and the cryoprotectant ethylene glycol, replacing the indole ring of the mutated tryptophan. (B) Inter-domain hydrogen bonds that have been mutated.

FIGS. 11A-C are graphs relating to the determination of ^(true)K_(d) and ^(app)K_(d) values for glucose in ttGGBP182C.2.0 (see Table 5). (A) Glucose dependence of the fluorescence emission intensities for the ttGGBP182C.2.0⋅Acrylodan mutant conjugate (see Table 4). Arrows indicate direction of change with increased glucose concentrations. (B) Determination of ^(app)K_(d) using ratiometry the emission intensities (R) at 475 nm and 545 nm (20 nm bandwidth). (C) Determination of ^(true)K_(d) by monochromatic fits the two ratiometric intensities (I(λ): green, 475 nm; red, 545 nm). Values for ^(app)K_(d) (4.5 mM) and ^(true)K_(d) (6.0 mM) were simultaneously fit to the three experimental binding isotherms using equations 1 and 5 using constant baselines for both the apo- and saturated protein, with the two monochromatic isotherms sharing the same ^(true)K_(d) value.

FIGS. 12A and B are graphs showing that a sensor arrays that combine several ttGGBP mutants (Table 6) could span the full pathophysiological range at better than 90% of maximal possible precision. (A) Mutants in the ttGGBP182C Acrylodan background. The responses are shown as relative precision, calculated from the fits to the experimental data according to equation 8, from left to right: ttGBP182C, hypoglycemia; ttGGBP182C.2.0, euglycemia; ttGGBP182C.2.3, mild hyperglycemia; ttGGBP182C.8, severe hyperglycemia; ttGGBP182C.9, hyperosmolar hyperglycemic state. (B) Mutants in the ttGGBP17C Badan background. Ratiometric signals are shown from left to right: ttGGBP 17C⋅Acrylodan (^(app)K_(d)=0.06 mM), ttGGBP 17C.1⋅Badan (^(app)K_(d)=1.2 mM), ttGGBP 17C.3⋅Badan (^(app)K_(d)=3.9 mM), ttGGBP 17C.5⋅Badan (^(app)K_(d)=19.3 mM). Black circles: experimental data points

FIG. 13 is a set of cartoons showing fusion constructs for sensor immobilization. Light gray, ttGGBP182C.2.0; diagonal striped, hexa-lysine immobilization tag; dark gray, hexa-histidine affinity purification tag; horizontal striped, ZF-QNK zinc finger domain; vertical striped, truncated zinc finger βZif domain; wavy line, Gly-Gly-Ser linker (two segments, indicate Gly-Gly-Ser-Gly-Gly-Ser). Left column, names of constructs.

FIGS. 14A-F are graphs showing that the immobilization of ttGGBP182C2.0⋅Acrylodan does not affect its thermostability. Thermostabilities were determined by measuring the ratio fluorescence emission intensities through 488 nm and 510 nm filters as a function of temperature in a Roche LightCycler. Panels A-C: ttGBP182C.2.0-Imm0; Panels D-F: ttGBP182C.2.0-Imm1 (see FIG. 13). (A) Solution (T_(m)=347.6K). (B) Immobilized on Nickel-nitriloacetic acid (Ni-NTA) beads (T_(m)=346.7K). (C) Reconstituted, desiccated Ni-NTA beads (T_(m)=347.6K). (D) Fluorescence response of ttGGBP5 2 Imm1 immobilized on NHS-functionalized agarose beads. Data was collected on a Roche LightCycler real-time PCS instrument, recording emission intensities at 488 nm and 510 nm as a function of temperature in a 384-well microtiter plate. Wells contain beads with labelled, immobilized protein in hydrogel at different glucose concentrations. Temperature melts of twelve different wells. Apo protein thermostability as reported by the denaturation mid-point temperature is 349 K, similar to the protein free in solution. (E) The three-dimensional landscape showing ratiometric signal as a function of glucose concentration and temperature is essentially indistinguishable from the protein free in solution. (F) Representative Langmuir ligand-binding curve extracted from the three-dimensional data. The K_(d) (glucose) value at 25° C. is 4.8 mM, which is similar to the protein free in solution.

FIG. 15 is a graph of a glucose titration curve determined for magnetic Ni-NTA beads coated with immobilized ttGGBP182C2.0⋅Acrylodan. Data were highly precise, being reproducible<0.2% coefficient of variance.

FIGS. 16A-F are grapgs showing the singular value decomposition of the glucose-dependent corrected spectra of Acrylodan and Badan conjugates of Y11C, F17C and W182C mutants of ttGGBP. (A) Y11C⋅Acrylodan; (B) Y11C⋅Badan; (C) F17C⋅Acrylodan; (D) F17C⋅Badan; (E) F182C⋅Acrylodan; (F) F182C⋅Badan. Frequency transformations of the spectra (equation 11) were decomposed into principal components (equation 12). The contribution of the first component, C₁ (black), is largely invariant with glucose concentration, whereas the second component, C₂ (gray), encode accounts for the glucose-dependent changes in the spectra (component contributions are given in Table 1). Inserts, glucose dependence of the fractional contribution of each component (equation 13).

FIGS. 17A-F are graphs showing glucose dependence of electronic transitions in the fluorescence emission intensity spectra of Acrylodan and Badan conjugates of Y11C, F17C and W182C mutants of ttGGBP. (A) Y11C⋅Acrylodan; (B) Y11C⋅Badan; (C) F17C⋅Acrylodan; (D) F17C⋅Badan; (E) F182C⋅Acrylodan; (F) F182C⋅Badan. The emission intensities can be accounted for to a first approximation by two excited state electronic transitions (FIG. 16): a low-energy, green, S₁ (Acrylodan: 521±9 nm; Badan: 530±14 nm) and a high-energy, blue, S₂ (Acrylodan: 477±14 nm; Badan: 477±16 nm) transition. The S₁ transition is present in all spectra; S₂ is present in all the glucose-responsive and 36% of the non-responsive conjugates (Table 7 and 8). In conjugates that exhibit glucose-responsive changes in fluorescence emission intensities, glucose binding shifts the population of these excited states. At each titration point, the experimentally observed emission intensities were modeled with Gaussians fits (equation 14) for S₁ and S₂ electronic transition (model parameter values in Table 3). Experimental emission spectra and Gaussian fits are shown only for the apo-protein, and saturated glucose complex. Emission spectra: dashed black line, apo-protein; solid black line, glucose complex. Gaussians (S₁, green lines; S₂, blue lines): dashed lines, apo-protein; solid lines, glucose complex. Thin black lines: residuals (equation 16) at each titration point. Inserts show the population fractions (equation 15) of the S₁ and S₂ transitions extracted from the spectra at each titration point (black circles) fit to Langmuir binding isotherms (solid lines) with ^(app)K_(d) values constrained to be the same for both populations. As a first approximation, the wavelengths of S₁ or S₂ transitions are the same in apo-protein and the saturated glucose complex. The residuals indicate that this approximation does not hold for all conjugates, and a more extensive treatment is required in which the S₁ and S₂ are split into multiple transitions (see discussion below). Wavelength shifts occur if there is a significant redistribution of the two excited state populations in the apo-protein and the saturated ligand complexes. In the bathochromic ratiometric 182C⋅Acrylodan conjugate, the S₁ state dominates in the glucose complex (panel E); in the hypsochromic conjugates 17C⋅Badan (panel D) and 17C⋅Acrylodan (panel C), apo-proteins comprise a mixture of the two states, whereas their glucose complexes contain almost exclusively the S₂ state. In the hypsochromic 11C⋅Badan sensor (panel B), the system shifts from a predominantly S₁ in the absence of glucose to almost equally populated S₁ and S₂ states in the glucose complex. Shifts in the fraction of S₁ and S₂ populations also occur in conjugates that did not exhibit overt shifts in the wavelengths of their emission intensity maxima. For instance, neither 11C⋅Acrylodan nor 182C⋅Badan exhibited significant shifts in emission maxima upon binding glucose. Nevertheless, SVD analysis revealed similar changes in the variable C₂ component as observed for the overtly ratiometric sensors, but with a smaller contribution (FIG. 16A and F). Gaussian analysis revealed small shifts in the S₁ and S₂ populations in response to glucose (panel A and F). This pattern also was observed in other non-ratiometrically responsive conjugates (Table 7 and 8). Wavelength shifts were observed if the C₂ component constitutes>5% of the total contribution.

FIGS. 18A-H is a series of graphs showing Glucose dependence of the S₁ and S₂ electronic transition contributions to the fluorescence emission intensity spectra of E. coli GGBP Acrylodan and Badan conjugates. Color schemes, symbols and line representation as in FIGS. 2-4. 16C⋅Acrylodan: (A) emission spectra (hypsochromic) and ratiometric glucose-binding curve (inset: λ₁, 454 nm; λ₂, 540 nm; ^(app)K_(d), 1.0 mM); (C) singular value decomposition; (E) Gausssian fits and glucose dependence of the S₁ and S₂ populations (inset). 16C⋅Badan: (B) emission spectra (hypsochromic) and ratiometric glucose-binding curve (inset: λ₁, 465 nm; λ₂, 555 nm; ^(app)K_(d), 0.4 mM); (D) singular value decomposition; (F) Gausssian fits and glucose dependence of the S₁ and S₂ populations (inset). 182C⋅Acrylodan: (G) singular value decomposition; (H) Gausssian fits and glucose dependence of the S₁ and S₂ populations (inset).

FIGS. 19A-F are graphs showing glucose dependence of the absorption spectra of ttGGBP Acrylodan and Badan conjugates that undergo wavelength shifts in their fluorescence emission intensities in response to ligand binding. ttGGBP F17C⋅Badan: (A) Absorption spectra (red, no glucose; purple, saturating glucose; black, intermediate glucose concentrations). Hypsochromic response was modeled by fit of a Langmuir ligand-binding isotherm (equation 1) to ratiometric analysis of the absorption intensities (inset: λ₁, 390 nm; λ₂, 340 nm; ^(app)K_(d), 1.7 mM); (C) singular value decomposition (components: black, C₁; gray, C₂); (E) Fit of Gaussian representations of electronic transitions to absorption spectra (dashed black line, apo-protein; solid black line, glucose complex) of G₁ (386 nm green; apo-protein, dashed; glucose complex, solid) and G₂ (359 nm, blue; apo-protein, dashed; glucose complex, solid) ground state electronic transitions. Inset, glucose dependence of population fractions at each glucose titration (black circles) of the G₁ and G₂ transitions fit to Langmuir binding isotherms (solid lines) with ^(app)K_(d) values constrained to be the same for both populations (residuals, thin lines). ttGGBP F182C⋅Acrylodan (color scheme, line representations, symbols, as above): (B) Absorption spectra (bathochromic response) and glucose binding (inset: λ₁, 375 nm; λ₂, 430 nm; ^(app)K_(d), 1.1 mM; ^(true)K_(d), 1.9 mM); (D) singular value decomposition; (F) G₁ and G₂ electronic transitions and populations. The residuals indicate that the maximal wavelength of the G₁ and G₂ transitions is different in the apo-protein and glucose (also see legend to FIG. 17).

FIG. 20 shows the sequence of an exemplary csaGGBP (Table 2) expression construct (SEQ ID NO: 105).

FIG. 21 shows the sequence of an exemplary bprGGBP (Table 2) expression construct (SEQ ID NO: 106).

FIG. 22 shows the sequence of an exemplary rinGGBP_A (Table 2) expression construct (SEQ ID NO: 107).

FIG. 23 shows the sequence of an exemplary fprGGBP (Table 2) expression construct (SEQ ID NO: 108).

FIG. 24 shows the sequence of an exemplary cljGGBP (Table 2) expression construct (SEQ ID NO: 109).

FIG. 25 shows the sequence of an exemplary cauGGBP (Table 2) expression construct (SEQ ID NO: 110).

FIG. 26 shows the sequence of an exemplary rinGGBP_B (Table 2) expression construct (SEQ ID NO: 111).

FIG. 27 shows the sequence of an exemplary erhGGBP (Table 2) expression construct (SEQ ID NO: 112).

FIG. 28 shows the sequence of an exemplary ereGGBP (Table 2) expression construct (SEQ ID NO: 113).

FIG. 29 shows the sequence of an exemplary ttGGBP (Table 2) expression construct (SEQ ID NO: 114).

FIG. 30 shows the sequence of an exemplary cobGGBP (Table 2) expression construct (SEQ ID NO: 115).

FIG. 31 shows the sequence of an exemplary chyGGBP (Table 2) expression construct (SEQ ID NO: 116).

FIG. 32 shows the sequence of an exemplary pspGGBP (Table 2) expression construct (SEQ ID NO: 117).

FIG. 33 shows the sequence of an exemplary ttGGBP11C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 118).

FIG. 34 shows the sequence of an exemplary ttGGBP16C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 119).

FIG. 35 shows the sequence of an exemplary ttGGBP17C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 120).

FIG. 36 shows the sequence of an exemplary ttGGBP42C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 121).

FIG. 37 shows the sequence of an exemplary ttGGBP67C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 122).

FIG. 38 shows the sequence of an exemplary ttGGBP91C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 123).

FIG. 39 shows the sequence of an exemplary ttGGBP92C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 124).

FIG. 40 shows the sequence of an exemplary ttGGBP111C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 125).

FIG. 41 shows the sequence of an exemplary ttGGBP148C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 126).

FIG. 42 shows the sequence of an exemplary ttGGBP151C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 127).

FIG. 43 shows the sequence of an exemplary ttGGBP152C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 128).

FIG. 44 shows the sequence of an exemplary ttGGBP181C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 129).

FIG. 45 shows the sequence of an exemplary ttGGBP182C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 130).

FIG. 46 shows the sequence of an exemplary ttGGBP183C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 131).

FIG. 47 shows the sequence of an exemplary ttGGBP257C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 132).

FIG. 48 shows the sequence of an exemplary ttGGBP259C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 133).

FIG. 49 shows the sequence of an exemplary ttGGBP300C Cysteine Scan Mutant (Table 3) expression construct (SEQ ID NO: 134).

FIG. 50 shows the sequence of an exemplary ttGGBP17C.1 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 135).

FIG. 51 shows the sequence of an exemplary ttGGBP17C.2 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 136).

FIG. 52 shows the sequence of an exemplary ttGGBP17C.3 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 137).

FIG. 53 shows the sequence of an exemplary ttGGBP17C.4 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 138).

FIG. 54 shows the sequence of an exemplary ttGGBP17C.5 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 139).

FIG. 55 shows the sequence of an exemplary ttGGBP17C.6 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 140).

FIG. 56 shows the sequence of an exemplary ttGGBP17C.7 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 141).

FIG. 57 shows the sequence of an exemplary ttGGBP17C.8 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 142).

FIG. 58 shows the sequence of an exemplary ttGGBP17C.9 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 143).

FIG. 59 shows the sequence of an exemplary ttGGBP17C.10 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 144).

FIG. 60 shows the sequence of an exemplary ttGGBP17C.11 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 145).

FIG. 61 shows the sequence of an exemplary ttGGBP17C.19 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 146).

FIG. 62 shows the sequence of an exemplary ttGGBP17C.20 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 147).

FIG. 63 shows the sequence of an exemplary ttGGBP17C.21 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 148).

FIG. 64 shows the sequence of an exemplary ttGGBP17C.22 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 149).

FIG. 65 shows the sequence of an exemplary ttGGBP17C.23 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 150).

FIG. 66 shows the sequence of an exemplary ttGGBP17C.24 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 151).

FIG. 67 shows the sequence of an exemplary ttGGBP17C.25 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 152).

FIG. 68 shows the sequence of an exemplary ttGGBP17C.26 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 153).

FIG. 69 shows the sequence of an exemplary ttGGBP17C.27 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 154).

FIG. 70 shows the sequence of an exemplary ttGGBP17C.28 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 155).

FIG. 71 shows the sequence of an exemplary ttGGBP17C.29 Affinity-Tuning Mutant (17C background) (Table 6) expression construct (SEQ ID NO: 156).

FIG. 72 shows the sequence of an exemplary ttGGBP182C.2.0 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 157).

FIG. 73 shows the sequence of an exemplary ttGGBP182C.2.1 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 158).

FIG. 74 shows the sequence of an exemplary ttGGBP182C.2.3 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 159).

FIG. 75 shows the sequence of an exemplary ttGGBP182C.2.4 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 160).

FIG. 76 shows the sequence of an exemplary ttGGBP182C.2.5 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 161).

FIG. 77 shows the sequence of an exemplary ttGGBP182C.2.6 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 162).

FIG. 78 shows the sequence of an exemplary ttGGBP182C.2.7 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 163).

FIG. 79 shows the sequence of an exemplary ttGGBP182C.2.8 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 164).

FIG. 80 shows the sequence of an exemplary ttGGBP182C.2.9 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 165).

FIG. 81 shows the sequence of an exemplary ttGGBP182C.3 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 166).

FIG. 82 shows the sequence of an exemplary ttGGBP182C.4 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 167).

FIG. 83 shows the sequence of an exemplary ttGGBP182C.5 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 168).

FIG. 84 shows the sequence of an exemplary ttGGBP182C.6 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 169).

FIG. 85 shows the sequence of an exemplary ttGGBP182C.7 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 170).

FIG. 86 shows the sequence of an exemplary ttGGBP182C.8 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 171).

FIG. 87 shows the sequence of an exemplary ttGGBP182C.9 Affinity-Tuning Mutant (182C background) (Table 6) expression construct (SEQ ID NO: 172).

FIG. 88 is a cartoon illustrating non-limiting aspects of continuous glucose monitoring.

FIG. 89 is a cartoon illustrating a non-limiting example of sample analysis with a biosensor.

DETAILED DESCRIPTION

Fluorescently responsive sensors (FRSs) based on engineered proteins that couple ligand-binding events to changes in the emission properties of intrinsic or semi-synthetically incorporated chromophores have wide-ranging applications in cell biology and analytical chemistry. If the fluorescence emission spectrum of an engineered FRS changes shape in response to ligand binding such that the ratio of intensities at two appropriately chosen wavelengths reports on ligand concentration (dichromatic response), then ratiometric measurements can be used to monitor analyte concentrations. Ratiometry Advantage is essential for devices that rely on changes in fluorescence emission intensities, because it provides an internally consistent reference. The self-calibrating nature of a ratiometric measurement removes the necessity for carrying out on-board calibration tests prior to each measurement, obviating the need for multiple components and fluidic circuitry. Accordingly, reagentless, ratiometric fluorescent sensors have many uses in process engineering, environmental or clinical chemistry, including single-use point-of-care applications, wearable devices, or implanted “tattoos” that are interrogated transdermally.

The periplasmic binding protein (PBP) superfamily provide a rich source of FRSs, because PBPs combine a large diversity of ligand specificities with a common structural mechanism that is well suited to the construction of fluorescence signal transduction schemes. The three-dimensional PBP monomer structure comprises two α/β domains linked by a β-strand hinge FIG. 1A. Binding of ligand is accompanied by a large hinge-bending motion that transitions the protein from an open to a closed state in which the ligand is enveloped within a cleft between the two domains. Semi-synthetic FRSs can be engineered with PBPs by site-specifically attaching single, thiol-reactive, environmentally sensitive fluorophores that respond to the ligand-mediated conformational change (FIGS. 1A-C). Here we describe the construction of robust, ratiometric, fluorescently responsive glucose sensors derived from thermostable members of a family of glucose-binding PBPs.

Glucose monitoring is essential for the management of diabetes mellitus, a disease that affects at least 366 million people world-wide, increasing every year. The majority of current glucose-monitoring technologies rely on enzymes for which glucose is one of the substrates. Glucose concentration measurements are therefore subject to variations in second substrate concentrations consumed in the enzyme reaction, such as oxygen in the case of glucose oxidase. Additional complications arise in systems where reaction rates are measured for enzymes immobilized on electrodes. In such arrangements, accuracy is compromised by factors that alter the rate at which glucose arrives at the electrode surface interfere with accuracy, such as hematocrit levels, or surface “fouling” by deposition of proteins and cells in the foreign body response. Ratiometric fluorescent glucose sensors obviate these problems, and accordingly have been incorporated successfully in optodes for continuous glucose monitoring in animals and humans.

In FRS-based sensors, signals arise from reversible binding equilibria of the analyte (ligand) to a receptor. These signals are most precise at ligand concentrations that match the receptor ligand-disassociation constant. Precision is maintained to within ˜80% of this maximal level over a concentration range approximately 3-fold above or below this point. Construction of effective FRS therefore requires matching of ligand-binding affinities to the relevant analyte concentrations. Arrays of multiple sensors may have to be used in concert to cover wide concentration ranges. Clinically relevant glucose levels vary approximately 100-fold (from ˜1 mM in extreme hypoglycemia, to ˜100 mM for the hyperosmolar, hyperglycemic condition, with healthy, euglycemic levels at ˜6 mM(Association 2000 Clinical Diabetes, 18; Pasquel 2014 Diabetes Care, 37, 3124-3131), requiring an array of multiple FRS sensors with distinct glucose affinities to report directly on the full range of clinically relevant glucose concentrations with high precision. Here we report a set of appropriately tuned thermostable, glucose-responsive FRSs, constructed by mutating their glucose-binding site.

Immobilization of FRSs on solid surfaces with minimal perturbation of the molecular sensing mechanism is an important step for incorporating biosensors into devices. Immobilization enables retention of the sensor within the sampling element (e.g. optode surface or implanted bead for in vivo sensing applications; or in a sample-handling cartridge for ex vivo sensing) Immobilization also may provide spatial localization to provide the necessary addressability of different elements in a multi-sensor array comprising sensors that differ in their engineered affinities for coverage of a wide range of glucose concentrations, or sensors that each detect distinct analytes.

Ex vivo clinical chemistries such as point-of-care applications require that the FRS is incorporated into a cartridge into which a sample is introduced at the time of measurement. Such “disposables” need to have a long shelf life that preferably does not require temperature control (e.g. refrigeration) for storage or distribution. It is preferable to incorporate immobilized protein in a stable, dried form in such disposables. The inherent resistance to denaturation of thermostable proteins minimizes the need for temperature control during manufacturing and storage, and may extend to the long-term stability of a desiccated state. The protein sensors described herein meet these requirements.

The spectral response, binding affinity, and thermostability of the robust thermostable glucose FRSs reported here are maintained following site-specific immobilization on a substrate such as beads. Furthermore, these properties are recovered rapidly upon reconstitution following drying and prolonged storage under accelerated aging conditions. These engineered proteins therefore are useful for high-precision, wide-dynamic range glucose sensing applications, including continuous monitoring, point-of-care, wearable sensor systems.

Biosensors

Biosensors are molecular recognition elements that transduce ligand-binding events into physical signals. Biosensors as detailed herein bind at least one ligand and emit a signal. A ligand-bound biosensor results in a signal that is different from the unbound biosensor. This difference facilitates detection of the at least one ligand and/or determination of ligand concentration. The biosensors may be used without the assistance of other reagents.

Described herein are novel engineered biosensors. These biosensors may have altered ligand-binding affinities, tailored ligand-binding specificities, and/or temperature dependencies of ligand binding or stability. For example, the herein described engineered glucose and galactose biosensors provide high-accuracy information related to extended glucose concentration ranges.

Binding of ligand mediates conformational changes in the biosensor, such as hinge-bending motions of the polypeptide. The conformational changes affect the environment of the reporter such that a change in the reporter-generated signal occurs. That is, without ligand bound, the biosensor results in signal generated from the reporter, and when ligand is bound, the signal generated from the reporter changes. The ligand-bound biosensor results in a reporter-generated signal that is different from the unbound biosensor.

In some embodiments, the methods and compositions include a plurality of a single type of biosensor. The biosensors may be identical in structure and function. For example, the biosensors of a single type may have the same polypeptide, the same reporter, and the same ligand affinity.

In other embodiments, the methods and compositions include a plurality of different types of biosensors. A plurality of these different types of biosensors may be arranged or incorporated in a panel. As used herein, a “panel” refers to two or more biosensors. The two or more biosensors may be different from each other. The biosensors may differ in structure and/or function. Biosensors may differ in polypeptide sequence, reporter, ligand affinities, or a combination thereof. Accordingly, there may be different types of biosensors. In some embodiments, each biosensor in the panel comprises the same reporter group. In some embodiments, each biosensor in the panel comprises a different reporter group. The panel may include at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, at least 80, at least 85, at least 90, at least 95, or at least 100 biosensors.

The panel of biosensors includes at least one sensor element. “Sensor element” refers to a single spot, site, location, or well for the at least one biosensor, to which a sample or aliquot thereof may be applied. The panel may be a composite sensor or an array.

In some embodiments, the panel is a composite sensor. In a composite sensor, each sensor element includes a mixture of two or more different biosensors. In some embodiments, the composite sensor includes one sensor element. In some embodiments, the composite sensor includes two or more sensor elements. In some embodiments, signals are measured from a composite sensor in which the signals arise from one or more biosensors in the sensor element. For example, signals may be measured from a composite sensor in which the signals arise from a subset of the total number of biosensors in the sensor element. For example, signals may be measured from a composite sensor in which the signals arise from two of five biosensors in the sensor element.

In some embodiments, the panel is an array. In an array, each sensor element includes a single type of biosensor. An array comprises a plurality of individually and spatially localized sensor elements. Each sensor element includes a biosensor that is different than or the same as the biosensor of a different sensor element. In some embodiments, signals are measured from an array in which the signals arise separately from two or more selected biosensors in separate sensor elements. An array may comprise a plurality of sensor elements of a variety of sizes and configurations. An array may comprise a plurality of sensor elements arranged linearly. For example, an array may comprise a plurality of micrometer-sized sensor elements arranged in a single row. An array may comprise a plurality of sensor elements arranged in a grid. The grid may be two- or three-dimensional. In some embodiments, the grid is a spatially addressable grid. In some embodiments, the biosensors are incorporated into an array, such as a multichannel or multiplexed array.

The biosensors of the present disclosure can be used in any setting where glucose detection is required or desired, such a medical setting (e.g., determining the level of blood glucose in a subject), environmental setting (e.g., determining the level of glucose in an environmental sample), biological setting (e.g., determining the presence or amount of glucose in a reaction), or in process engineering, such as monitoring the amount of glucose in a fermentation reaction (e.g., beer/wine production, etc.). Other examples include, but are not limited to, uses in the food industry (Suleiman et al, In: Biosensor Design and Application: Mathewson and Finley Eds; American Chemical Society, Washington, D.C. 1992, vol. 511); in clinical chemistry (Wilkins et al., Med. Eng. Phys. 1996, 18, 273-288; Pickup, Tr. Biotech. 1993, 11, 285-291; Meyerhoff et al., Endricon 1966, 6, 51-58; Riklin et al., Nature 1995, 376, 672-675); Willner et al., J. Am. Chem. Soc. 1996, 118, 10321-10322); as the basis for the construction of a fluorescent flow cell containing immobilized GGBP-FAST conjugates (see, e.g., Wilkins et al., Med. Eng. Phys. 1966, 18, 273-288; Pickup, Tr. Biotech. 1993, 11, 285-291; Meyerhoff et al., Endricon. 1966, 6, 51; Group, New Engl. J. Med. 1993, 329, 977-986; Gough et al., Diabetes 1995, 44, 1005-1009); and in an implantable devices, such as those suitable for use as an artificial pancreas.

The biosensors as detailed herein may be administered in a variety of ways known by those of skill in the art, as appropriate for each application. Biosensors may be provided in a solution. The solution may be buffered. Biosensors may be provided in a solution and mixed directly with a sample. In some embodiments, a biosensor is immobilized onto a surface. Biosensors may be immobilized within a disposable cartridge into which a sample may be introduced or applied. Biosensors may be implanted or incorporated in a wearable device. The biosensor may be provided as an optode.

The biosensor may be attached to or incorporated in a wearable device. Wearable devices may include, for example, adhesive strips, patches, and contact lenses. The biosensor may be configured for placement in contact with a subject's skin or mucosal surface. In some embodiments, the biosensor is configured as an adhesive strip. In some embodiments, the biosensor is configured within or on the surface of a contact lens. In some embodiments, the contact lens is formed from a transparent substrate shaped to be worn directly over a subject's eye, as described in, for example, U.S. Pat. No. 8,608,310.

The biosensor may be implanted. The biosensor may be implanted in a subject's body. The biosensor may be implanted in a subject's blood vessel, vein, eye, natural or artificial pancreas, skin, or anywhere in the alimentary canal including the stomach, intestine and esophagus. The biosensor may be implanted in a subject with a microbead. In some embodiments, the biosensor is configured to be implanted in the skin. The biosensor may be implanted in a subject sub-dermally. The biosensor may generate the signal trans-dermally. In some embodiments, the biosensor may be implanted in a subject with transdermal microbeads, wherein the optical signals can be transmitted remotely between the biosensor and detecting device.

In some embodiments, the biosensor is administered as an optode. As used herein, “optode” refers to an optical fiber with a single biosensor, or a composite biosensor, immobilized at the surface or at the end. An “optode” may also be referred to as an “optrode.” In some embodiments, the biosensor is implanted in a subject as an optode. The optode may be incorporated with or into a needle. The optode may be incorporated with a probe such as endoscopy or colonoscopy probes. The optode may be used in a tumor, near a tumor, or at the periphery of a tumor. In some embodiments, the biosensor may be implanted in a subject as an optode, wherein the optical signals can be transmitted between the biosensor and detecting device using physical links. In some embodiments, the biosensor is administered as an optode to a sample or reaction. The optode may be contacted with a sample or reaction. In some embodiments, an optode is used to continuously or episodically monitor a ligand in a sample or reaction.

Methods of Detecting the Presence of a Ligand

Provided herein is a method of detecting the presence of a ligand in a sample. The method may include contacting the biosensor with the sample; measuring a signal from the biosensor; and comparing the signal to a ligand-free control. A difference in signal indicates the presence of ligand in the sample.

Also provided herein is a method of detecting the presence of glucose in a sample. The method may include (a) providing a glucose biosensor disclosed herein in which the reporter group is attached the GGBP so that a signal transduced by the reporter group when the GGBP is bound to glucose differs from a signal transduced by the reporter group when the GGBP is not bound to glucose; (b) contacting the biosensor with the test sample under conditions such that the biosensor can bind to glucose present in the test sample; and (c) comparing the signal transduced by the reporter group when the biosensor is contacted with the test sample with the signal transduced by the reporter group when the biosensor is contacted with a glucose-free control sample, wherein a difference in the signal transduced by the reporter group when the biosensor is contacted with the test sample, as compared to when the biosensor is contacted with the control sample, indicates that the test sample contains glucose.

Methods of Determining the Concentration of a Ligand

Provided herein is a method of determining the concentration of a ligand in a sample. The method may include contacting the biosensor with the sample; measuring a signal from the biosensor; and comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

Another aspect of the present disclosure provides a method of determining the concentration of glucose in a test sample comprising, consisting of, or consisting essentially of: (a) providing a glucose biosensor comprising a glucose biosensor as described herein in which the reporter group is attached the GGBP so that a signal transduced by the reporter group when the GGBP is bound to glucose differs from a signal transduced by the reporter group when the GGBP is not bound to glucose; (b) contacting the biosensor with the test sample under conditions such that the biosensor can bind to glucose present in the test sample; and (c) comparing the signal transduced by the reporter group when the biosensor is contacted with the test sample with a standard hyperbolic glucose binding curve prepared by measuring the signal transduced by the reporter group when the biosensor is contacted with control samples containing known quantities of glucose to determine the concentration of glucose in the test sample.

Methods of Monitoring the Presence of a Ligand

The present invention is directed to a method of episodically or continuously monitoring the presence of a ligand in a reaction. In certain embodiments, the biosensors may be used in the continuous monitoring of glucose in a reaction. In certain embodiments, the glucose sensors may be used in episodic monitoring of sample aliquots.

The method of episodically or continuously monitoring the presence of a ligand in a reaction may include contacting the biosensor with the reaction; maintaining the reaction under conditions such that the polypeptide is capable of binding ligand present in the reaction; and episodically or continuously monitoring the signal from the biosensor in the reaction.

The method of episodically or continuously monitoring the presence of a ligand in a reaction may include contacting the biosensor with the reaction; maintaining the reaction under conditions such that the polypeptide is capable of binding ligand present in the reaction; episodically or continuously monitoring the signal from the biosensor in the reaction; and comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

In some embodiments, the method further includes comparing the signal to a ligand-free control, wherein a difference in signal indicates the presence of ligand in the reaction.

In some embodiments, the method further includes comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

Another aspect of the present disclosure provides a method of continuously monitoring the presence of glucose in a reaction comprising, consisting of, or consisting essentially of: (a) providing a glucose biosensor as described herein in which the reporter group is attached the GGBP so that a signal transduced by the reporter group when the GGBP is bound to glucose differs from a signal transduced by the reporter group when the GGBP is not bound to glucose; (b) maintaining the biosensor within the reaction and under conditions such that the biosensor can bind to glucose present in the reaction; (c) continuously monitoring the signal transduced by the reporter group when the biosensor is contacted with the glucose present in the reaction; and optionally (d) comparing the signal transduced by the reporter group when the biosensor is contacted with the glucose present in the reaction with the signal transduced by the reporter group when the biosensor is contacted with a glucose-free control sample, wherein a difference in the signal transduced by the reporter group when the biosensor is contacted with the glucose present in the reaction, as compared to when the biosensor is contacted with the control sample, indicates glucose is present in the reaction.

Yet another aspect of the present disclosure provides a method of continuously monitoring the concentration of glucose in a reaction comprising, consisting of, or consisting essentially of: (a) providing a glucose biosensor comprising a glucose biosensor as described herein in which the reporter group is attached the GGBP so that a signal transduced by the reporter group when the GGBP is bound to glucose differs from a signal transduced by the reporter group when the GGBP is not bound to glucose; (b) maintaining the biosensor within the reaction under conditions such that the biosensor can bind to glucose present in the reaction; and (c) continuously monitoring the signal transduced by the reporter group when the biosensor is contacted with the glucose present in the reaction; and (d) comparing the signal transduced by the reporter group when the biosensor is contacted with the glucose present in the reaction with a standard hyperbolic glucose binding curve prepared by measuring the signal transduced by the reporter group when the biosensor is contacted with control samples containing known quantities of glucose to determine the concentration of glucose in the reaction.

General Definitions

Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in cell culture, molecular genetics, and biochemistry).

As used herein, the term “about” in the context of a numerical value or range means ±10% of the numerical value or range recited or claimed, unless the context requires a more limited range.

In the descriptions above and in the claims, phrases such as “at least one of” or “one or more of” may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” In addition, use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible

It is understood that where a parameter range is provided, all integers within that range, and tenths thereof, are also provided by the invention. For example, “0.2-5 mg” is a disclosure of 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg etc. up to and including 5.0 mg.

A small molecule is a compound that is less than 2000 daltons in mass. The molecular mass of the small molecule is preferably less than 1000 daltons, more preferably less than 600 daltons, e.g., the compound is less than 500 daltons, 400 daltons, 300 daltons, 200 daltons, or 100 daltons.

As used herein, an “isolated” or “purified” nucleic acid molecule, polynucleotide, polypeptide, or protein, is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. Purified compounds are at least 60% by weight (dry weight) the compound of interest. Preferably, the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight the compound of interest. For example, a purified compound is one that is at least 90%, 91%, 92%, 93%, 94%, 95%, 98%, 99%, or 100% (w/w) of the desired compound by weight. Purity is measured by any appropriate standard method, for example, by column chromatography, thin layer chromatography, or high-performance liquid chromatography (HPLC) analysis. A purified or isolated polynucleotide (ribonucleic acid (RNA) or deoxyribonucleic acid (DNA)) is free of the genes/nucleic acids or sequences/amino acids that flank it in its naturally-occurring state. Purified also defines a degree of sterility that is safe for administration to a human subject, e.g., lacking infectious or toxic agents. In the case of tumor antigens, the antigen may be purified or a processed preparation such as a tumor cell lysate.

Similarly, by “substantially pure” is meant a nucleotide or polypeptide that has been separated from the components that naturally accompany it. Typically, the nucleotides and polypeptides are substantially pure when they are at least 60%, 70%, 80%, 90%, 95%, or even 99%, by weight, free from the proteins and naturally-occurring organic molecules with they are naturally associated.

The transitional term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. By contrast, the transitional phrase “consisting of” excludes any element, step, or ingredient not specified in the claim. The transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.

“Subject” as used herein refers to any organism from which a biological sample is obtained. For example, the sample is a biological fluid or tissue. For example, a subject is one who wants or is in need of detecting ligand or determining the concentration of ligand with the herein described biosensors. The subject may be a human or a non-human animal. The subject may be a mammal. The mammal may be a primate or a non-primate. The mammal can be a primate such as a human; a non-primate such as, for example, dog, cat, horse, cow, pig, mouse, rat, camel, llama, goat, rabbit, sheep, hamster, and guinea pig; or non-human primate such as, for example, monkey, chimpanzee, gorilla, orangutan, and gibbon. The subject may be of any age or stage of development, such as, for example, an adult, an adolescent, or an infant.

As used herein, an “expression vector” is a DNA or RNA vector that is capable of effecting expression of one or more polynucleotides. Preferably, the expression vector is also capable of replicating within the host cell. Expression vectors can be either prokaryotic or eukaryotic, and are typically include plasmids. Expression vectors of the present invention include any vectors that function (i.e., direct gene expression) in host cells of the present invention, including in one of the prokaryotic or eukaryotic cells described herein, e.g., gram-positive, gram-negative, pathogenic, non-pathogenic, commensal, cocci, bacillus, or spiral-shaped bacterial cells; archaeal cells; or protozoan, algal, fungi, yeast, plant, animal, vertebrate, invertebrate, arthropod, mammalian, rodent, primate, or human cells. Expression vectors of the present invention contain regulatory sequences such as transcription control sequences, translation control sequences, origins of replication, and other regulatory sequences that are compatible with the host cell and that control the expression of a polynucleotide. In particular, expression vectors of the present invention include transcription control sequences. Transcription control sequences are sequences which control the initiation, elongation, and termination of transcription. Particularly important transcription control sequences are those which control transcription initiation such as promoter, enhancer, operator and repressor sequences. Suitable transcription control sequences include any transcription control sequence that can function in at least one of the cells of the present invention. A variety of such transcription control sequences are known to those skilled in the art.

As used herein, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a disease,” “a disease state”, or “a nucleic acid” is a reference to one or more such embodiments, and includes equivalents thereof known to those skilled in the art and so forth.

As used herein, “pharmaceutically acceptable” carrier or excipient refers to a carrier or excipient that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio. It can be, e.g., a pharmaceutically acceptable solvent, suspending agent or vehicle, for delivering the instant compounds to the subject.

The term “diagnosis” refers to a determination that a disease is present in the subject. Similarly, the term “prognosis” refers to a relative probability that a certain future outcome may occur in the subject. For example, in the context of the present disclosure, prognosis can refer to the likelihood that an individual will develop a disease, or the likely severity of the disease (e.g., severity of symptoms, rate of functional decline, survival, etc.).

Depending on context, the terms “polypeptide” and “protein” may be used interchangeably.

A polypeptide or class of polypeptides may be defined by the extent of identity (% identity) of its amino acid sequence to a reference amino acid sequence, or by having a greater % identity to one reference amino acid sequence than to another. A variant of any of genes or gene products disclosed herein may have, e.g., 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid or amino acid sequences described herein. The term “% identity,” in the context of two or more nucleic acid or polypeptide sequences, refers to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. For example, % identity is relative to the entire length of the coding regions of the sequences being compared, or the length of a particular fragment or functional domain thereof. Variants as disclosed herein also include homologs, orthologs, or paralogs of the genes or gene products described herein. In some embodiments, variants may demonstrate a percentage of homology or identity, for example, at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity conserved domains important for biological function, e.g., in a functional domain, e.g. a ligand-binding or catalytic domain.

For sequence comparison, one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Percent identity is determined using BLAST. For the BLAST searches, the following parameters were employed: (1) Expect threshold is 10; (2) Gap cost is Existence:11 and Extension:1; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is “on.”

The present invention also provides for functional fragments of the genes or gene products described herein. A fragment of a protein is characterized by a length (number of amino acids) that is less than the length of the full length mature form of the protein. A fragment, in the case of these sequences and all others provided herein, may be a part of the whole that is less than the whole. Moreover, a fragment ranges in size from a single nucleotide or amino acid within a polynucleotide or polypeptide sequence to one fewer nucleotide or amino acid than the entire polynucleotide or polypeptide sequence. Finally, a fragment is defined as any portion of a complete polynucleotide or polypeptide sequence that is intermediate between the extremes defined above.

For example, fragments of any of the proteins or enzymes disclosed herein or encoded by any of the genes disclosed herein can be 10 to 20 amino acids, 10 to 30 amino acids, 10 to 40 amino acids, 10 to 50 amino acids, 10 to 60 amino acids, 10 to 70 amino acids, 10 to 80 amino acids, 10 to 90 amino acids, 10 to 100 amino acids, 50 to 100 amino acids, 75 to 125 amino acids, 100 to 150 amino acids, 150 to 200 amino acids, 200 to 250 amino acids, 250 to 300 amino acids, or 300 to 350 amino acids. The fragments encompassed in the present subject matter comprise fragments that retain functional fragments. As such, the fragments preferably retain the binding domains that are required or are important for functional activity. Fragments can be determined or generated by using the sequence information herein, and the fragments can be tested for functional activity using standard methods known in the art. For example, the encoded protein can be expressed by any recombinant technology known in the art and the binding activity of the protein can be determined.

As used herein a “biologically active” fragment is a portion of a polypeptide which maintains an activity of a full-length reference polypeptide. Biologically active fragments as used herein exclude the full-length polypeptide. Biologically active fragments can be any size as long as they maintain the defined activity. Preferably, the biologically active fragment maintains at least 10%, at least 50%, at least 75% or at least 90%, of the activity of the full length protein.

Amino acid sequence variants/mutants of the polypeptides of the defined herein can be prepared by introducing appropriate nucleotide changes into a nucleic acid defined herein, or by in vitro synthesis of the desired polypeptide. Such variants/mutants include, for example, deletions, insertions or substitutions of residues within the amino acid sequence. A combination of deletion, insertion and substitution can be made to arrive at the final construct, provided that the final peptide product possesses the desired activity and/or specificity.

Mutant (altered) peptides can be prepared using any technique known in the art. For example, a polynucleotide defined herein can be subjected to in vitro mutagenesis or DNA shuffling techniques as broadly described by Harayama (1998). Products derived from mutated/altered DNA can readily be screened using techniques described herein to determine if they possess, for example, glucose and/or galactose binding activity.

In designing amino acid sequence mutants, the location of the mutation site and the nature of the mutation will depend on characteristic(s) to be modified. The sites for mutation can be modified individually or in series, e.g., by (1) substituting first with conservative amino acid choices and then with more radical selections depending upon the results achieved, (2) deleting the target residue, or (3) inserting other residues adjacent to the located site.

Amino acid sequence deletions generally range from about 1 to 15 residues, more preferably about 1 to 10 residues and typically about 1 to 5 contiguous residues. In some embodiments, a mutated or modified protein does not comprise any deletions or insertions. In various embodiments, a mutated or modified protein has less than about 10, 9, 8, 7, 6, 5, 4, 3, or 2 deleted or inserted amino acids.

Substitution mutants have at least one amino acid residue in the polypeptide molecule removed and a different residue inserted in its place. Sites may be substituted in a relatively conservative manner in order to maintain activity and/or specificity. Such conservative substitutions are shown in the table below under the heading of “exemplary substitutions.”

In certain embodiments, a mutant/variant polypeptide has only, or not more than, one or two or three or four conservative amino acid changes when compared to a naturally occurring polypeptide. Details of conservative amino acid changes are provided in the table below. As the skilled person would be aware, such minor changes can reasonably be predicted not to alter the activity of the polypeptide when expressed in a recombinant cell.

Exemplary Substitutions Original Residue Exemplary Substitutions Alanine (Ala) Val; Leu; Ile; Gly Arginine (Arg) Lys Asparagine (Asn) Gln; His Cysteine (Cys) Ser Glutamine (Gln) Asn; His Glutamic Acid (Glu) Asp Glycine (Gly) Pro; Ala Histidine (His) Asn; Gln Isoleucine (Ile) Leu; Val; Ala Leucine (Leu) Ile; Val; Met; Ala; Phe Lysine (Lys) Arg Methionine (Met) Leu; Phe Phenylalanine (Phe) Leu; Val; Ala Proline (Pro) Gly Serine (Ser) Thr Threonine (Thr) Ser Tryptophan (Trp) Tyr Tyrosine (Tyr) Trp; Phe Valine (Val) Ile; Leu; Met; Phe; Ala

Mutations can be introduced into a nucleic acid sequence such that the encoded amino acid sequence is altered by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. Certain amino acids have side chains with more than one classifiable characteristic. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, tryptophan, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tyrosine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in a given polypeptide is replaced with another amino acid residue from the same side chain family Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a given coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for given polypeptide biological activity to identify mutants that retain activity. Conversely, the invention also provides for variants with mutations that enhance or increase the endogenous biological activity. Following mutagenesis of the nucleic acid sequence, the encoded protein can be expressed by any recombinant technology known in the art and the activity/specificity of the protein can be determined. An increase, decrease, or elimination of a given biological activity of the variants disclosed herein can be readily measured by the ordinary person skilled in the art, i.e. , by measuring the capability for binding a ligand and/or signal transduction.

In various embodiments, a polypeptide comprises mutations such that 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or less than about 10, 9, 8, 7, 6, 5, 4, 3, or 2 amino acids is substituted with a cysteine and/or a lysine.

Polypeptides can be produced in a variety of ways, including production and recovery of natural polypeptides or recombinant polypeptides according to methods known in the art. In one embodiment, a recombinant polypeptide is produced by culturing a cell capable of expressing the polypeptide under conditions effective to produce the polypeptide, such as a host cell defined herein.

Key to the Sequence Listing SEQ ID NO Sequence Name 1 ecGGBP [U.S. National Center for Biotechnology Information (NCBI) Accession No. WP_032329053] 2 ttGGBP (NCBI Accession Nos. YP_003852930.1 and WP_013298803.1) 3 stGGBP (NCBI Accession No. WP_001036943) 4 chyGGBP (NCBI Accession Nos. WP_013402088.1 and YP_003991244.1) 5 cobGGBP (NCBI Accession Nos. WP_013289482.1 and YP_003839461.1) 6 pspGGBP (NCBI Accession Nos. WP_015735911.1 and YP_003243743.1) 7 csaGGBP (NCBI Accession Nos. WP_013273028.1 and YP_003822565.1) 8 bprGGBP (NCBI Accession Nos. WP_013280279.1 and YP_003830205.1) 9 rinGGBP_A (NCBI Accession Nos. WP_006855636.1 and YP_007778116.1) 10 fprGGBP (NCBI Accession Nos. WP_015536639.1 and YP_007799070.1) 11 cljGGBP (NCBI Accession No. CLJU_c08950) 12 cauGGBP (NCBI Accession No. CAETHG_2989) 13 rinGGBP_B (NCBI Accession Nos. WP_006855628.1 and YP_007778124.1) 14 erhGGBP (NCBI Accession Nos. WP_003775352.1 and YP_004561181.1) 15 ereGGBP (NCBI Accession Nos. WP_012741392.1 and YP_002936409.1) 16 ecGGBP (with signal peptide replaced with M) 17 ecGGBP (with signal sequence removed) 18 ttGGBP (with signal peptide replaced with M) 19 stGGBP (with signal peptide replaced with M) 20 chyGGBP (with signal peptide replaced with M) 21 cobGGBP (with signal peptide replaced with M) 22 pspGGBP (with signal peptide replaced with M) 23 csaGGBP (with signal peptide replaced with M) 24 bprGGBP (with signal peptide replaced with M) 25 rinGGBP_A (with signal peptide replaced with M) 26 fprGGBP (with signal peptide replaced with M) 27 cljGGBP (with signal peptide replaced with M) 28 cauGGBP (with signal peptide replaced with M) 29 rinGGBP_b (with signal peptide replaced with M) 30 erhGGBP (with signal peptide replaced with M) 31 ereGGBP (with signal peptide replaced with M) 32 ecGGBPW183C (with signal peptide replaced with M; a W183C mutation; and a GGSHHHHHH at C-terminus) 33 ecGGBP (with signal peptide replaced with M and a GGSHHHHHH at C- terminus) 34 csaGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 35 bprGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 36 rinGGBP_A (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 37 fprGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 38 cljGGBP (with signal peptide replaced with M and a GGSHHHHHH at C- terminus) 39 cauGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 40 rinGGBP_B (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 41 erhGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 42 ereGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 43 ttGGBP (with signal peptide replaced with M and a GGSHHHHHH at C- terminus) 44 cobGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 45 chyGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 46 pspGGBP (with signal peptide replaced with M and a GGSHHHHHH at C-terminus) 47 cobGGBP.W181C (Signaling cys mutant of cobGGBP with signal peptide replaced with M and GGSHHHHHH at C-terminus) 48 chyGGBP.W181C (Signaling cys mutants of chyGGBP with signal peptide replaced with M and GGSHHHHHH at C-terminus) 49 ttGGBP11C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 50 ttGGBP16C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 51 ttGGBP17C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 52 ttGGBP42C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 53 ttGGBP67C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 54 ttGGBP91C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 55 ttGGBP92C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 56 ttGGBP111C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 57 ttGGBP148C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 58 ttGGBP151C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 59 ttGGBP152C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 60 ttGGBP181C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 61 ttGGBP182C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 62 ttGGBP183C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 63 ttGGBP257C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 64 ttGGBP259C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 65 ttGGBP300C (ttGGBP cys mutant with signal peptide replaced with M and GGSHHHHHH at C-terminus) 66 ttGGBP17C.1 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 67 ttGGBP17C.2 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 68 ttGGBP17C.3 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 69 ttGGBP17C.4 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 70 ttGGBP17C.5 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 71 ttGGBP17C.6 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 72 ttGGBP17C.7 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 73 ttGGBP17C.8 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 74 ttGGBP17C.9 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 75 ttGGBP17C.10 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 76 ttGGBP17C.11 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 77 ttGGBP17C.19 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 78 ttGGBP17C.20 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 79 ttGGBP17C.21 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 80 ttGGBP17C.22 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 81 ttGGBP17C.23 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 82 ttGGBP17C.24 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 83 ttGGBP17C.25 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 84 ttGGBP17C.26 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 85 ttGGBP17C.27 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 86 ttGGBP17C.28 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 87 ttGGBP17C.29 (affinity-tuning mutant, 17C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 88 ttGGBP182C.2.0 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 89 ttGGBP182C.2.1 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 90 ttGGBP182C.2.3 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 91 ttGGBP182C.2.4 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 92 ttGGBP182C.2.5 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 93 ttGGBP182C.2.6 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 94 ttGGBP182C.2.7 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 95 ttGGBP182C.2.8 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 96 ttGGBP182C.2.9 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 97 ttGGBP182C.3 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 98 ttGGBP182C.4 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 99 ttGGBP182C.5 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 100 ttGGBP182C.6 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 101 ttGGBP182C.7 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 102 ttGGBP182C.8 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 103 ttGGBP182C.9 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M and GGSHHHHHH at C-terminus) 104 GGSHHHHHH 105 csaGGBP Exemplary Expression Construct (Table 2) 106 bprGGBP Exemplary Expression Construct (Table 2) 107 rinGGBP_A Exemplary Expression Construct (Table 2) 108 fprGGBP Exemplary Expression Construct (Table 2) 109 clj GGBP Exemplary Expression Construct (Table 2) 110 cauGGBP Exemplary Expression Construct (Table 2) 111 rinGGBP_B Exemplary Expression Construct (Table 2) 112 erhGGBP Exemplary Expression Construct (Table 2) 113 ereGGBP Exemplary Expression Construct (Table 2) 114 ttGGBP Exemplary Expression Construct (Table 2) 115 cobGGBP Exemplary Expression Construct (Table 2) 116 chyGGBP Exemplary Expression Construct (Table 2) 117 pspGGBP23 Exemplary Expression Construct (Table 2) 118 ttGGBP11C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 119 ttGGBP16C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 120 ttGGBP17C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 121 ttGGBP42C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 122 ttGGBP67C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 123 ttGGBP91C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 124 ttGGBP92C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 125 ttGGBP111C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 126 ttGGBP148C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 127 ttGGBP151C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 128 ttGGBP152C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 129 ttGGBP181C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 130 ttGGBP182C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 131 ttGGBP183C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 132 ttGGBP257C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 133 ttGGBP259C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 134 ttGGBP300C Exemplary Cysteine Scan Mutant Expression Construct (Table 3) 135 ttGGBP17C.1 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 136 ttGGBP17C.2 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 137 ttGGBP17C.3 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 138 ttGGBP17C.4 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 139 ttGGBP17C.5 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 140 ttGGBP17C.6 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 141 ttGGBP17C.7 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 142 ttGGBP17C.8 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 143 ttGGBP17C.9 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 144 ttGGBP17C.10 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 145 ttGGBP17C.11 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 146 ttGGBP17C.19 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 147 ttGGBP17C.20 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 148 ttGGBP17C.21 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 149 ttGGBP17C.22 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 150 ttGGBP17C.23 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 151 ttGGBP17C.24 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 152 ttGGBP17C.25 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 153 ttGGBP17C.26 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 154 ttGGBP17C.27 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 155 ttGGBP17C.28 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 156 ttGGBP17C.29 Exemplary Affinity-Tuning mutant (17C Background) Expression Construct (Table 6) 157 ttGGBP182C.2.0 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 158 ttGGBP182C.2.1 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 159 ttGGBP182C.2.3 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 160 ttGGBP182C.2.4 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 161 ttGGBP182C.2.5 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 162 ttGGBP182C.2.6 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 163 ttGGBP182C.2.7 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 164 ttGGBP182C.2.8 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 165 ttGGBP182C.2.9 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 166 ttGGBP182C.3 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 167 ttGGBP182C.4 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 168 ttGGBP182C.5 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 169 ttGGBP182C.6 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 170 ttGGBP182C.7 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 171 ttGGBP182C.8 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 172 ttGGBP182C.9 Exemplary Affinity-Tuning mutant (182C Background) Expression Construct (Table 6) 173 ttGGBP182C.2.0_Imm0 174 ttGGBP, R91K,Q148E 175 ttGGBP182C.2.0_Imm1 176 ttGGBP182C.2.0_Imm2 177 ttGGBP182C.2.0_Imm3 178 ttGGBP182C.2.0_Imm4 179 ttGGBP182C.2.0_Imm5 180 ttGGBP182C.2.0_Imm6 181 ttGGBP182C.2.0_Imm7 182 IYKXDDXFM (Conserved Sequence) 183 YKXDDXFM (Conserved Sequence) 184 YKXDDXF (Conserved Sequence) 185 KXDDXF (Conserved Sequence) 186 YKXDD (Conserved Sequence) 187 KXDD (Conserved Sequence) 188 DDXF (Conserved Sequence) 189 DXFMXXVR (Conserved Sequence) 190 DXFMXXV (Conserved Sequence) 191 DXFM (Conserved Sequence) 192 IYKXDNXFM (Conserved Sequence) 193 YKXDNXFM (Conserved Sequence) 194 YKXDNXF (Conserved Sequence) 195 KXDNXF (Conserved Sequence) 196 YKXDN (Conserved Sequence) 197 KXDN (Conserved Sequence) 198 DNXF (Conserved Sequence) 199 NXFMXXVR (Conserved Sequence) 200 NXFMXXV (Conserved Sequence) 201 NXFM (Conserved Sequence) 202 PVVFFNKEP (Conserved Sequence) 203 PVVFXNKEP (Conserved Sequence) 204 PVVFFNXEP (Conserved Sequence) 205 PVVFXNXEP (Conserved Sequence) 206 VVFXNXEP (Conserved Sequence) 207 VFXNXEP (Conserved Sequence) 208 PVVFXNXE (Conserved Sequence) 209 PVVFXN (Conserved Sequence) 210 PXVFXN (Conserved Sequence) 211 PVXFXN (Conserved Sequence) 212 FXNXEP (Conserved Sequence) 213 FXNXE (Conserved Sequence) 214 PGHPDAEART (Conserved Sequence) 215 PGHXDAXXRT (Conserved Sequence) 216 GHXDAXXRT (Conserved Sequence) 217 HXDAXXRT (Conserved Sequence) 218 DA)OCRT (Conserved Sequence) 219 PGHXDAXXR (Conserved Sequence) 220 PGHXDA (Conserved Sequence) 221 PGHXD (Conserved Sequence) 222 PGNPDAEART (Conserved Sequence) 223 PGNXDAXXRT (Conserved Sequence) 224 GNXDAXXRT (Conserved Sequence) 225 NXDAXXRT (Conserved Sequence) 226 PGNXDAXXR (Conserved Sequence) 227 PGNXDA (Conserved Sequence) 228 PGNXD (Conserved Sequence) 229 DTAMWD (Conserved Sequence) 230 DTAMCD (Conserved Sequence) 231 DTAMW (Conserved Sequence) 232 DTAMC (Conserved Sequence) 233 TAMWD (Conserved Sequence) 234 TAMCD (Conserved Sequence) 235 AXWXX (Conserved Sequence) 236 AXCXX (Conserved Sequence) 237 IEVVIANND (Conserved Sequence) 238 EVVIANND (Conserved Sequence) 239 IEVVIANN (Conserved Sequence) 240 EVVIANN (Conserved Sequence) 241 IEXVXXNND (Conserved Sequence) 242 IEXVXXNN (Conserved Sequence) 243 EXVXXNND (Conserved Sequence) 244 EXVXXNN (Conserved Sequence) 245 PVFGVDA (Conserved Sequence) 246 VFGVDA (Conserved Sequence) 247 PVFGVD (Conserved Sequence) 248 FGVDA (Conserved Sequence) 249 PVXGVDA (Conserved Sequence) 250 VXGVDA (Conserved Sequence) 251 PVXGVD (Conserved Sequence) 252 VXGVD (Conserved Sequence) 253 GTVLNDA (Conserved Sequence) 254 GTVLND (Conserved Sequence) 255 GTVLN (Conserved Sequence) 256 TVLND (Conserved Sequence) 257 chyGGBP_F12C (chGGBP with signal sequence replaced with M; F12C, C39A, and C206A mutations; and GGSHHHHHH at C-terminus) 258 chyGGBP_F16C (chGGBP with signal sequence replaced with M; F16C, C39A, and C206A mutations; and GGSHHHHHH at C-terminus) 259 chyGGBP_W181C (chGGBP with signal sequence replaced with M; W181C, C39A, and C206A mutations; and GGSHHHHHH at C-terminus) cobGGBP_F12C (cobGGBP with signal sequence replaced with M; 260 F12C, C39A, C173A, and C206A mutations; and GGSHHHHHH at C- terminus) 261 cobGGBP_F16C (cobGGBP with signal sequence replaced with M; F16C, C39A, C173A, and C206A mutations; and GGSHHHHHH at C- terminus) 262 cobGGBP_W181C (cobGGBP with signal sequence replaced with M, W181C, C39A, C173A, and C206A mutations; and GGSHHHHHH at C- terminus) 263 pspGGPB_F13C (pspGGBP with signal sequence replaced with M; F13C mutation; and GGSHHHHHH at C-terminus) 264 pspGGPB_F9C (pspGGBP with signal sequence replaced with M; F9C mutation; and GGSHHHHHH at C-terminus) 265 pspGGPB_W178C (pspGGBP with signal sequence replaced with M; W178C mutation; and GGSHHHHHH at C-terminus) 266 csaGGBP_F18C (csaGGBP with signal sequence replaced with M; F18C, C62A, C82A, C113A, and C211A mutations; and GGSHHHHHH at C- terminus) 267 csaGGBP_W186C (csaGGBP with signal sequence replaced with M; W186C, C62A,C82A,C113A, and C211A mutations; and GGSHHHHHH at C-terminus) 268 csaGGBP_Y14C (csaGGBP with signal sequence replaced with M; Y14C, C62A,C82A,C113A, and C211A mutations; and GGSHHHHHH at C-terminus) 269 bprGGBP_F16C (bprGGBP with signal sequence replaced with M; F16C, C8A, C112A, C116A, C179A, C211A, and C289A mutations; and GGSHHHHHH at C-terminus) 270 bprGGBP_K12C (bprGGBP with signal sequence replaced with M; K12C, C8A, C112A, C116A, C179A, C211A, and C289A mutations; and GGSHHHHHH at C-terminus) 271 bprGGBP_W187C (bprGGBP with signal sequence replaced with M; W187C, C8A, C112A, C116A, C179A, C211A, and C289A mutations; and GGSHHHHHH at C-terminus) 272 rinGGBP_A_F10C (rinGGBP_A with signal sequence replaced with M; F10C, C6A, C114A, C177A, C210A, and C288A mutations; and GGSHHHHHH at C-terminus) 273 rinGGBP_A_F14C (rinGGBP_A with signal sequence replaced with M; F14C, C6A, C114A, C177A, C210A, and C288A mutations; and GGSHHHHHH at C-terminus) 274 rinGGBP_A_W185C (rinGGBP_A with signal sequence replaced with M; W185C, C6A, C114A, C177A, C210A, and C288A mutations; and GGSHHHHHH at C-terminus) 275 rinGGBP_B_F17C (rinGGBP_B with signal sequence replaced with M; F17C, C66A, C70A, and C306A; and GGSHHHHHH at C-terminus) 276 rinGGBP_B_Q13C (rinGGBP_B with signal sequence replaced with M; Q13C, C66A, C70A, and C306A mutations; and GGSHHHHHH at C- terminus) 277 rinGGBP_B_W189C (rinGGBP_B with signal sequence replaced with M; W189C, C66A, C70A, and C306A mutations; and GGSHHHHHH at C- terminus) 278 fprGGBP_F12C (fprGGBP with signal sequence replaced with M; F12C, C8A, C105A, C106A, C143A, and C205A mutations; and GGSHHHHHH at C-terminus) 279 fprGGBP_F16C (fprGGBP with signal sequence replaced with M; F16C, C8A, C105A, C106A, C143A, and C205A mutations; and GGSHHHHHH at C-terminus) 280 fprGGBP_W180C (fprGGBP with signal sequence replaced with M; W180C, C8A, C105A, C106A, C143A, and C205A mutations; and GGSHHHHHH at C-terminus) 281 cljGGBP_Fl1C (cljGGBP with signal sequence replaced with M; F11C, C77A, and C198A mutations; and GGSHHHHHH at C-terminus) 282 cljGGBP_W15C (cljGGBP with signal sequence replaced with M; W15C, C77A, and C198A mutations; and GGSHHHHHH at C-terminus) 283 cljGGBP_W176C (cljGGBP with signal sequence replaced with M; W176C, C77A, and C198A mutations; and GGSHHHHHH at C-terminus) 284 cauGGBP_F12C (cauGGBP with signal sequence replaced with M; F12C, C78A, and C199A mutations; and GGSHHHHHH at C-terminus) 285 cauGGBP_W16C (cauGGBP with signal sequence replaced with M; W16C, C78A, and C199A mutations; and GGSHHHHHH at C-terminus) 286 cauGGBP_W177C (cauGGBP with signal sequence replaced with M; W177C, C78A, and C199A mutations; and GGSHHHHHH at C-terminus) 287 erhGGBP_F13C (erhGGBP with signal sequence replaced with M; F13C mutation; and GGSHHHHHH at C-terminus) 288 erhGGBP_F17C (erhGGBP with signal sequence replaced with M; F17C mutation; and GGSHHHHHH at C-terminus) 289 erhGGBP_W188C (erhGGBP with signal sequence replaced with M; W188C mutation; and GGSHHHHHH at C-terminus) 290 ereGGBP_F17C (ereGGBP with signal sequence replaced with M; F17C, C10A, C29A, C65A, C69A, and C183A mutations; and GGSHHHHHH at C-terminus) 291 ereGGBP_Q13C (ereGGBP with signal sequence replaced with M; Q13C, ClOA, C29A, C65A, C69A, and C183A mutations; and GGSHHHHHH at C-terminus) 292 ereGGBP_W188C (ereGGBP with signal sequence replaced with M; W188C, C10A, C29A, C65A, C69A, and C183A mutations; and GGSHHHHHH at C-terminus) 293 r3Zif 294 ZF-QNK 295 Hexahistidine Tag 296 Hexalysine Tag 297 ecGGBP.F16C (with signal peptide replaced with M; a F16C mutation; and a GGSHHHHHH at C-terminus) 298 ttGGBP182C.2.0 (affinity-tuning mutant, 182C background (Table 6) with signal peptide replaced with M)

Examples are provided below to facilitate a more complete understanding of the invention. The following examples illustrate the exemplary modes of making and practicing the invention. However, the scope of the invention is not limited to specific embodiments disclosed in these Examples, which are for purposes of illustration only, since alternative methods can be utilized to obtain similar results.

EXAMPLE 1 Fluorescently Responsive Sensor Engineering Phases

The engineering of FRSs can be divided into five phases:

-   -   1. Binding protein discovery. A set of glucose-binding protein         sequence homologs is identified. Accurate assignment of their         ligand-binding function utilizes application of a prediction         method that incorporates information encoded in the         experimentally determined three-dimensional structure of         periplasmic glucose-binding proteins.     -   2. Experimental lead validation. Synthetic genes are         constructed, which are optimized for heterologous expression in         Escherichia coli of one or more predicted glucose-binding         protein sequences. The glucose-binding properties and         thermostabilities of the corresponding expressed, purified         proteins are evaluated.     -   3. Engineering of fluorescent responses. Semisynthetic         fluorescent conjugates of the experimentally validated leads are         constructed by attaching fluorophores to single cysteine         mutants. The effect of glucose binding on the fluorescence         emission properties of those conjugates is evaluated. Those         conjugates that evince strong, ratiometric responses are         selected as FRSs.     -   4. Affinity tuning. Single or multiple mutations are introduced         by site-directed mutagenesis to alter the glucose-binding         affinities of glucose-responsive FRSs. A set of FRS variants is         selected that together cover the clinical glucose concentration         range with high accuracy.     -   5. Device integration. FRSs are immobilized in the sampling         component of the analytical device in a manner that preserves         their fluorescent response and glucose affinity. Long-term         storage conditions are established.

EXAMPLE 2 Identification of a Family of Periplasmic Glucose-Binding Proteins Homologs Using Structurally Assisted Function Evaluation (Phase Step 1)

As a first step in constructing robust glucose sensor candidates, we examined bacterial genomic sequences to identify periplasmic glucose-binding protein sequences in known thermophiles. Homologs from such organisms are likely to encode thermostable proteins. Analysis of enzyme families has shown that overall sequence identity below ˜60% is a weak predictor of function conservation (Todd 2001 J. Mol. Biol., 307, 1113-1143; Tian 2003 J. Mol. Biol., 333, 863-882). Furthermore, functional assignments based on sequence homology alone are known to be particularly problematic in the PBP superfamily For instance, PBPs that by overall sequence identity are predicted to bind oligopeptides were found to bind oligosaccharides. Enzyme functional assignments are improved greatly if a sequence selection filter based on conservation of catalytic residues identified from protein structures is included. Such catalytic residues comprise a subset of all the residues that contact an enzyme substrate or inhibitor. In the case of the PBPs, functional selection filters need to take into account all the protein-ligand contacts that encode the ligand-binding function. Accordingly, we have developed a structurally assisted functional evaluation (SAFE) method to identify PBP sequence homologs with accurately predicted function. The SAFE homolog search method consists of five steps encoded in the ProteinHunter software package:

-   -   1. Sequence homolog set is collected using the BLAST sequence         alignment tool(Altschul et al. 1990) with standard settings         (expect threshold: 10.0; gap cost existence: 11; gap extension:         1; substitution matrix: Blosum62; filter for low complexity         regions on), starting with Escherichia coli periplasmic         glucose-galactose binding protein (ecGGBP) sequence (SEQ ID         NO: 17) as a seed (Vyas, Vyas and Quiocho 1988 Science, 242,         1290-5). The ProteinHunter program selects only those pairwise         BLAST alignments that (a) share a minimum of 20% sequence         identity, and (b) have 70% coverage of their entire sequence         length by the aligned region. This set of sequences defines a         universe of possible glucose-binding proteins without assigning         function.     -   2. Structure-based encoding of biological function. A PCS         comprising the protein residues that form hydrogen bonds and van         der Waals contacts with the bound glucose is defined using         computer-assisted, visual inspection of the three-dimensional         structure of the ecGGBP-glucose complex. ProteinHunter         identifies if the calculated distance between any of their atoms         and any glucose atom is less than 5 Å, and the distances between         their backbone C_(α) and any atom in glucose is greater than         that of their C_(β) atom and any atom in glucose. Secondary         shell residues that do not form hydrogen bonds or van der Waals         contacts are removed by inspection from the resulting set. The         choice of allowed residues is guided by the identity of the         residue in the structure, and mutants that are likely to         maintain that interaction. The resulting definition specifies         residue positions and their permitted amino acid identity.         Multiple amino acid identities are permitted at each position to         encode functionally equivalent residues. This definition         establishes a search filter for the accurate prediction of         glucose-binding proteins within the universe of sequence         homologs collected in (1).     -   3. Accurate sequence alignment. Tools such as ClustalW (Chenna         et al. 2003 Nucleic Acids Res, 31, 3497-500) are used to         construct an accurate alignment of all the sequence homologs.         The ecGGBP seed sequence is included in this alignment. This         multiple sequence alignment establishes the equivalent positions         of the ecGGBP PCS in each sequence homolog.     -   4. Function evaluation. The glucose-binding properties of each         of the aligned sequence homologs is determined by measuring         their compliance with the PCS sequence filter. A “Hamming         distance”, H, is assigned for each homolog by the ProteinHunter         program, which specifies the degree of sequence identity of all         the residues at the aligned PCS positions. A value of H=0         indicates that the identities of all the residues at the aligned         PCS positions match the amino acid(s) allowed in the PCS search         filter; H>0, indicates that one or more aligned positions have         disallowed residues. Sequences for which H=0 are predicted to         encode glucose-binding proteins.     -   5. Selection of representative SAFE homologs. The sequence         homologs are ordered by (a) identity with the seed PCS, as         measured by the Hamming distance, (b) fractional overall         sequence identity with the seed sequence. A subset for sequences         with H=0, sampling the fractional overall sequence identity is         selected for experimental verification.

The ProteinHunter software tool encodes the flow of execution, applies the PCS search filter, and visualizes the results that include organism annotations such as thermophilicity, and Gram stain status.

These steps are encoded in the ProteinHunter software tool, which encodes the flow of execution, applies the PCS search filter, and visualizes the results, and handles organism annotations such as thermophilicity, and Gram stain status.

Annotated genomic and plasmid sequences of 5062 prokaryotes were downloaded from the National Center of Biotechnology Information (download date: May 17, 2015; ftp://ftp.ncbi.nih.gov/genomes/Bacteria/all.gbk.tar.gz). The protein sequence for the E. coli glucose-galactose binding protein (ecGGBP) was extracted from the protein structure file 2gbp(Vyas et al. 1988 Science, 242, 1290-5), and used as the seed sequence for the BLAST search described above. A total of 1822 sequence homologs were identified.

In ecGGBP, glucose binding is encoded by a PCS comprising ten residues. Two aromatic residues (F16, W182) sandwich the bound glucose through extensive van der Waals interactions with either surface of the pyranose ring. The other eight residues form hydrogen bonds with all the glucose hydroxyls. A PCS filter specifying multiple amino acids at these 10 positions was used to predict glucose-binding proteins (FIGS. 2A-C). A total of 139 homologs were predicted to encode glucose-binding proteins, on the basis of their Hamming distance scores (H=0). The overall sequence identities of these homologs relative to the ecGGBP seed varied from 100% to 29% (Table 1).

EXAMPLE 3 Lead Protein Validation Using Ligand-Mediated Thermostability Shifts (Phase Step 2)

Thirteen homologs that were predicted to be glucose-binding proteins (FIG. 3) were selected to probe different degrees of sequence identity to the ecGGBP seed, and their glucose-binding properties were determined experimentally (Table 2). These experiments comprise four successive steps:

-   -   1. Synthetic gene construction. The amino acid sequence of the         homology leads are backtranslated into DNA sequences. These are         optimized for directing heterologous cytoplasmic expression of         the protein homologues in E. coli, using either the OrfOpt,         (U.S. Patent Publication No. 2011/0171737), hereby incorporated         by reference or OrfMorph (described herein) programs. These         programs predict mRNA sequences that direct high-level protein         expression in E. coli. The predicted gene sequences are         assembled de novo from synthetic oligonucleotides.     -   2. Heterologous protein expression of the homologues in E. coli.         Plasmids carrying the synthetic expression constructs (see         above) were transformed into KRX (E. coli K12 Derivative Strain)         competent cells (Promega, Technical Bulletin TB352). Protein         production was induced in bacterial cultures of these cultures,         as described in the Materials and Methods.     -   3. Purification of successfully expressed protein using         immobilized metal affinity chromatography, as described in         Materials and Methods.     -   4. Verification of glucose binding. Determination of the         glucose-binding properties of the purified proteins using a         thermal stability shift assay, as described in Materials and         Methods.         Seven of the thirteen synthetic expression constructs         successfully directed heterologous cytoplasmic expression of a         GGBP homolog in E. coli. The glucose-binding properties of five         of these were confirmed directly using the thermal shift assay         (FIGS. 4A-B). The thermostability of two homologs was too high         (^(apo)T_(m)>90° C.) for this assay to be applicable. Their         glucose-binding properties were confirmed by measuring the         temperature-dependent fluorescence responses of         Acrylodan-labeled single cysteine mutants (see section 5) to         glucose (FIGS. 5A-B).

Surprisingly, the sequence identity of all these experimentally verified glucose-binding homologs relative the ecGGBP seed are considerably below the 60% threshold, ranging from 29% to 48%. Several use alternate amino acids in the PCS at position 152, demonstrating the predictive power of allowing functionally equivalent residues. These results therefore demonstrate that biological function can be predicted accurately with the SAFE technique, even in sequence homologs with low fractional identities to the original seed.

Three of the experimentally verified GGBP homologs exhibit mid-point thermal denaturation temperatures (T_(m) values) in the 347-350 K range, which is at least 25 K more stable than the ecGGBP seed (T_(m)=322 K). Of these, the homolog from Thermoanaerobacter thermosaccharolyticum (ttGGBP) was produced at the highest level by heterologous expression in E. coli. This protein was selected as the candidate for constructing robust glucose sensors.

EXAMPLE 4 Cysteine Mutant Scans and Fluorophore Screening to Identify Fluorescently Responsive Glucose Sensors (Phase Step 3)

Semi-synthetic FRSs were engineered by site-specifically attaching thiol-reactive, environmentally sensitive fluorophores that respond to ligand-mediated conformational changes. Identification of FRS candidates that are useful for sensing applications comprises three steps:

-   -   1. Cysteine scan. Mutant glucose-binding proteins containing         single cysteines are constructed for site-specific attachment of         thiol-reactive fluorophores. Positions in PBPs where attached         single fluorophores are likely to exhibit ligand-dependent         responses were determined (de Lorimier et al. 2002 Protein Sci,         11, 2655-75). Candidate positions fall into three classes:         endosteric, replacing a residue that contacts the ligand         directly; peristeric, located at the rim of the binding site;         allosteric (Marvin et al. 1997 Proc Natl Acad Sci USA, 94,         4366-71; Marvin 1998 J Am Chem Soc, 120, 7-11), located outside         the binding site at sites that undergo local structural changes         in concert with the hinge-bending motion.     -   2. Fluorophore screening. Thiol-reactive, environmentally         sensitive fluorophores are attached to each cysteine mutant         prepared in step 1.     -   3. Evaluation of the glucose-mediated change of all the         fluorescent conjugates prepared in step 2. Responses to ligand         binding in which there is both a change in fluorescence emission         intensity and spectral shape was essential for chemometric         applications, because such changes enable ratiometric         measurements. Changes in spectral shape typically are         accompanied by a shift in the wavelength of the emission         intensity maxima. Three classes of fluorescent responses are         possible:         -   i. No response.         -   ii. Monochromatic response (emission intensity increases or             decreases without a change in spectral shape)         -   iii. Dichromatic response (both intensity and spectral shape             changes) which can be classified into two sub-classes:             -   i. Hypsochromatic: emission intensity shifts to shorter                 wavelengths upon binding glucose (“blue shift”).             -   ii. Bathochromatic: emission intensity shifts to longer                 wavelengths upon binding glucose (“red shift”).

We constructed seventeen single cysteine mutants in ttGGBP, exploring four endosteric, ten peristeric, and three allosteric positions (FIGS. 6A-B). At each position, we attached the Prodan-derived fluorophores such as Acrylodan and Badan, which differ by one methylene group in their thiol-reactive linking moiety. The fluorescence emission intensities of seven Acrylodan and five Badan conjugates responded to glucose at seven attachment positions (Table 3). At only four attachment positions were the responses of both fluorophores qualitatively similar, and never quantitatively. We also tested for glucose binding by measuring ligand-mediated shifts in protein thermal stability (Table 3). By this criterion, the majority of the non-responsive conjugates bound glucose. The two conjugates that did not bind glucose (N42C⋅Badan, V67C⋅Badan) also exhibited large losses in overall thermostability (28-30 K decrease in apo T_(m) values), indicating that the attached fluorophore adversely affected their structural integrity. By contrast, all other conjugates exhibited only small variations in apo-protein thermostability (1-4 K), indicating that the fluorophore causes minimal perturbations instability.

Endosteric attachment positions exhibited the most pronounced changes in fluorescence emissions in response to ligand binding. Conjugates at three of the ten peristeric positions were responsive to glucose. No allosteric conjugates exhibited fluorescence responses to glucose.

We observed ligand-dependent shifts in the wavelengths of emission intensity maxima at one peristeric (Y11C) and two endosteric (F17C, W182C) sites (FIGS. 7A-F), enabling dichromatic ratiometric measurements; the maximum intensity of other glucose-responsive conjugates remained the same (monochromatic responses). Wavelengths shifts occurred in both directions: in the ttGGBP W182C⋅Acrylodan conjugate the apo-protein spectrum converted from a short- to a long-wavelength emission state upon binding glucose (bathochromic shift), whereas the emissions in F17C⋅Acrylodan, F17C⋅Badan and Y11C⋅Badan conjugates shifted to shorter wavelengths (hypsochromic shift). The Badan and Acrylodan conjugates attached to F17C and W182C, respectively, exhibited the largest, wavelength-dependent changes in fluorescence emission intensities, (FIGS. 7A-C).

The responses to glucose of a number of other fluorophores (FIGS. 8A-P) were also tested at positions 182C and 17C (Table 4). Several conjugates exhibited significant changes in emission intensity upon glucose addition, but none of these were accompanied by large wavelengths shifts of their maxima. Both increases and decreases in fluorescence were observed.

The most effective sensors that were discovered are the Badan and Acrylodan conjugates attached to the endosteric cysteine mutations F17C and W182C, respectively. For example, peptides with SEQ ID No:61 (ttGGBP182C), SEQ ID NO:88 (ttGGBP182C.2.0), SEQ ID NO:90 (ttGGBP182C.2.3), and SEQ ID NO:102 (ttGGBP182C.8) are particularly useful for clinical diagnostics, because they span hypoglycemia, euglycemia, mild hyperglycemia, severe hyperglycemia, and hyperosmolar hyperglycemic glucose concentrations respectively. These two fluorophores differ only in their linker geometry, but this small difference determines whether dichromatic or monochromatic responses are observed for a particular conjugate. At position 17C, only the Badan and not the Acrylodan conjugate evinces a dichromatic response; at 182C; surprisingly, the reverse case is observed. Within a given bacterial periplasmic binding protein, some attachment sites are more effective than others, and within a given attachment site, some fluorophores are more effective than others (DeLorimier et al., 2002, Protein Science 11:2655-2675). Thus, the nature of the responses therefore is idiosyncratic, and therefore the choice of which site to mutate (e.g., substitute with a single cysteine) and which fluorophore to use at a particular site is nonobvious. Changes in linker geometry and chromophore modifications give rise to significant differences in the detailed interactions of particular fluorophores with the protein, even within families of closely related molecules, thereby significantly impacting sensor characteristics, consistent with previous observations.

EXAMPLE 5 Determination of Exemplary Fluorescent Conjugate Structures

The structures of the fluorescent conjugates with pronounced dichromatic responses, ttGGBP17C⋅Badan and ttGGBP182C.2.0⋅Acrylodan (SEQ ID NO: 88) (this is a variant in which the glucose-binding affinity has been manipulated), were determined by X-ray crystallography (Table 5; FIG. 9). The structure of the E. coli GGBP homolog conjugate, ecGGBP W183C⋅Acrylodan (ecGGBP W183C, SEQ ID NO: 32), was determined also.

Like all members of the periplasmic-binding protein (PBP) superfamily, GGBPs comprise two domains connected by a flexible hinge, with the ligand-binding site located in a cleft between the two domains. In the absence of ligand, PBPs adopt an open conformation, in which the two domains move apart and the cleft is wide. In ligand complexes, hinge-bending motions move the two domains closer together, forming a binding site that completely envelops the ligand, reminiscent of a protein interior. The overall structures of the ecGGBP and ttGGBP conjugates are similar with a backbone C_(α) RMSD of 0.6 Å and 0.9 Å for the N- and C-terminal domains respectively (C-terminal domain contains the Ca²⁺-binding site) as expected for proteins that are 48% identical (Chothia 1986 EMBO J., 5, 823-826). Small variations in the degree of closure can affect critical inter-domain hydrogen-bonding interactions. With the exception of mutated aromatic groups, the interactions between the protein and bound glucose are conserved. The structures of these conjugates enabled us to determine the interactions between the protein and the fluorophore and the internal conformation of the fluorophore. These sets of observations guided the choice of mutations for manipulating glucose affinities.

In both F17C⋅Badan and W182C⋅Acrylodan, the conjugated fluorophores point out into solution. A view down the long axis of ttGGBP from the C-terminal towards the N-terminal domain into the ligand-binding site reveals that three channels, each approximately 120° apart, connect the centrally located bound monosaccharide to the protein surface (FIG. 9c ). One channel is occupied by the R-group of the natural galactoside ligand (this position is occupied by water in the glucose and galactose complexes), the other two are filled by Badan and Acrylodan in their respective conjugates.

In the wild-type protein, the rings of F17 and W182 form extensive van der Waals contact with the bound glucose. The outward orientation of the fluorophore in the W182C⋅Acrylodan conjugate leaves a cavity vacated by the indole ring, which is filled with water and cryoprotectant. The cavity created by the loss of the smaller benzyl ring in F17C⋅Badan is largely filled with the linker; no water or cryoprotectant was observed.

The Acrylodan and Badan fluorophores contain two important internal degrees of freedom (FIGS. 6a-c ): the twist of the dimethylamino group, and the carbonyl. The state of these two angles influences the fluorescence properties of the fluorophore, by altering the extent of electronic conjugation within the system, and the degree of polarization of the excited dipole. The electron density of Badan in the ttGGBP F17C conjugate was well defined, enabling us to determine the internal fluorophore conformation with high confidence (FIG. 9d-f ). The dimethyl amino group is co-planar with the naphthalene ring. The carbonyl group is twisted out of plane by approximately 30°. By contrast, in ecGGBP.183C⋅Acrylodan the carbonyl is co-planar (FIG. 9g ). This group is probably also co-planar in the ttGGBP.182C⋅Acrylodan structure, but the partial occupancy of the conjugate in this structure precluded a definitive conclusion. Nevertheless, the high degree of similarity in structure and spectral properties of the ecGGBP 183C and ttGGBP 182C Acrylodan conjugates suggests that the Acrylodan carbonyl is co-planar in both homolog conjugates.

In both ttGGBP 17C⋅Badan and 182C⋅Acrylodan (and ecGGBP 183C⋅Acrylodan) conjugates, the pocket in which the fluorophore carbonyl is located comprises residues contributed by each domain, and is fully formed only in the closed, glucose-bound protein conformation. No hydrogen bonds are observed between the fluorophore carbonyl and the protein at either attachment position. In ttGGBP 17C⋅Badan the “knob” of the twisted carbonyl conformation is bound in a small “hole” formed by residues also contributed by both domains (FIG. 9h ). The carbonyl is held in place by van der Waals interactions proximal to the attachment site with residues located in the domain opposite to the F17C site: the C_(β) carbon of N258 touches the carbonyl; the backbone atoms of residues 239-241 interact with one of the two naphthalene rings faces. The twisted ttGGBP F17C⋅Badan conformation therefore is stabilized by interactions of the protein with both the naphthalene ring and the carbonyl. These interactions are fully formed in the closed state only. By contrast, in ecGGBP 183C⋅Acrylodan the carbonyl hole is not well defined. The carbonyl is flanked by E149 (same domain as attachment site), and K92 (opposite domain), but these residues form no direct contacts in the structure. Neither the carbonyl nor the naphthalene rings of this planar conjugate are constrained by clear interactions in the protein closed conformation.

EXAMPLE 6 Affinity Tuning (Phase Step 4)

Blood glucose concentrations range from ˜3 mM (hypoglycemia) to ˜30 mM (hyperglycemia) and up to ˜100mM for the hyperosmolar hyperglycemic state (HHS), with healthy levels at around 6 mM (euglycemia). Measurements using reagentless sensors are most sensitive at analyte concentrations that match the dissociation constant. The glucose affinity of ttGGBP182C⋅Acrylodan is too high and must therefore be “tuned” by raising the K_(d) value.

The mutations that alter glucose affinities fall into four classes:

-   -   1. Alteration of direct interactions in the PCS between the         protein and the bound glucose.     -   2. Manipulation of the equilibrium between the open and closed         states.     -   3. Alteration of interactions between the protein and the         fluorescent conjugate. Two sub-classes can be distinguished:         -   a. Interactions with the carbonyl group         -   b. Interactions with the naphthalene ring     -   4. Indirect interactions that alter the geometry of the binding         site.

Representatives of mutant classes 1-3 were constructed in the ttGGBP182C and ttGGBP17C backgrounds, using Acrylodan and Badan conjugates to evaluate their effects on glucose binding (Table 6).

Mutations in the PCS residues (Class 1) do not afford many opportunities for manipulating affinity subtly. Mutagenesis of ecGGBP has demonstrated that most PCS positions are intolerant of mutations, with the exception of histidine that interacts with the 6-hydroxyl, and the aspartate that binds the epimeric 4-hydroxyl. In ttGGBP182C⋅Acrylodan, the H151Q mutations subtly lower the affinity into the middle of the pathophysiological concentration range, whereas in ttGGBP17C⋅Badan H151Q lowers affinity, but nearly abolishes ratiometry. In ttGGBP182C⋅Acrylodan, D15N weakens glucose binding into the HHS range and increases discrimination between glucose and galactose. In ttGGBP17C⋅Badan, D15A weakens ligand binding and enhances the dichromatic response.

Uniquely in ttGGBP182C⋅Acrylodan, the PCS also can be manipulated by mutating position 154 adjacent to the cavity vacated by the missing indole ring of W182 (FIG. 10a ). Three mutations in Ala154 alter the affinity 50-fold, spanning the entire pathophysiological glucose concentration range. The A154M mutation increases the affinity ˜10-fold, presumably by (partially) restoring direct van der Waals interactions between the protein and bound glucose, which were lost upon removal of the tryptophan. The 154S mutation causes a 19 K decrease in thermostability; the other mutations exhibit negligible effects on thermostability.

The conformational equilibrium can be altered by manipulating those hydrogen bonds between the N- and C-terminal domains that are predicted to form in the closed, but not the open state (Class 2 mutations). Four locations form inter-domain hydrogen bonds in the protein closed conformation (FIG. 10b ) of ttGGBP: T16-D211, R69-G150 (main-chain), R91-Q148, and E92 (main-chain)-Q152. The first of these interactions is located between the Badan and Acrylodan channels, whereas the other three are positioned between the Acrylodan and galactoside R-group channels (FIG. 9c ). Disruption of inter-domain interactions alters the intrinsic equilibrium between the open and closed conformations, thereby decreasing ligand affinity. Accordingly, in the ttGGBP W182C⋅Acrylodan conjugate mutants, glucose affinities are lowered (K_(d) values raised) in the class 2 mutations. These mutations also alter the fluorescence emission spectra. In all the class 2 mutants of both ttGGBPF17C Acrylodan and Badan conjugates the spectral responses are altered, either enhancing or abolish wavelength shifts. These observations indicate that mutations of the inter-domain hydrogen bonds cause (small) changes in the structure of the closed state, which affect the fluorophore environment.

Mutations in the interactions between the protein and the conjugated fluorophore (Class 3 mutants), changing either the carbonyl hole (Class 3a) or the fluorophore channel walls (Class 3b), have large effects on glucose binding and fluorescence spectra. In ttGGBP17C⋅Badan, most of the N258 mutants in the carbonyl hole do not respond to glucose. The absence of shifts in thermal stability in the presence of glucose indicates that these mutants no longer bind ligand. The 17C⋅Acrylodan N258S mutant conjugate is the exception: it binds and responds to glucose, but binding does not evoke a fluorescent response. Mutations in residues located on either side of the channel wall strongly influence spectral properties of the fluorescent conjugates. In ttGGBP17C⋅Badan, with the exception of A260W, mutations in A260 convert dichromatic to monochromatic responses. In ttGGBP182C⋅Acrylodan, the behavior of mutations in the R91 andQ148 interaction is complex, because these potentially affect both inter-domain hydrogen bonding and interactions between the protein and the conjugated fluorophore. The fluorophore blocks the formation of R91K-Q148E in the ttGGBP182C.2.0⋅Acrylodan double mutant structure, but in ecGGBP183C⋅Acrylodan E149-K92 is present, reflecting subtle differences in fluorophore conformation and inter-domain closure angles. The two single Q148E and R91K mutants both exhibit a modest increase of glucose affinities in ttGGBP182C⋅Acrylodan, suggesting that this inter-domain is maintained, and slightly improved. By contrast, the Q148E+R91K double mutant exhibits a 2.6-fold decrease in affinity, consistent with the observed loss of interaction in the ttGGBP182C2.0⋅Acrylodan double mutant structure (SEQ ID NO: 88). The glucose affinity of the ttGGBP182C.2.0⋅Acrylodan double mutant (SEQ ID NO: 88) falls within the euglycemic concentration range (FIG. 13), which is why this variant was selected for structural analysis (FIG. 11).

Affinity-tuning mutations introduced in both the ttGGBP17C⋅Badan or ttGGBP182C⋅Acrylodan backgrounds yield a collection of dichromatic sensors that cover the wide range of glucose concentrations encountered in clinical chemistry.

EXAMPLE 7 Sensor Arrays for Detecting a Wide Range of Glucose Concentrations

The precision (reciprocal of the error) of individual sensor precision is maximal at the K_(d) value, and decreases at lower or higher glucose concentrations(Marvin et al. 1997 Proc Natl Acad Sci USA, 94, 4366-71). Construction of a high-precision sensor capable of spanning the entire 100-fold clinical concentration range from extreme hypoglycemia to the HHS therefore requires combining several sensors together to maintain a high precision level. In the ttGGBP182C⋅Acrylodan background, a suite of five affinity mutants can be combined that together provide high-precision coverage from 1-100 mM (FIG. 12). A suite of four mutants in the ttGGBP17C⋅Badan background provides similar coverage. It should be noted that the ttGGBP17C⋅Badan variants switch from dim green to bright blue upon binding glucose, whereas the ttGGBP182C⋅Acrylodan variants switch from bright blue to dim green. These opposing changes in color and brightness in response to glucose binding provide additional internal checks on the integrity of the observations in an array that combines sensors derived from both backgrounds.

EXAMPLE 8 Device Integration (Phase Step 5)

Protein immobilization on solid surfaces, e.g. a polymeric planar structure or bead structure, paper, glass, silica or metal, is an important step for incorporating biosensors into devices. Immobilization enables (i) spatial localization, (ii) control over the presentation of the sensors to the reader (e.g. by encoding geometries for optical readouts), (iii) selective retention in sample separation procedures. It is advantageous to control the geometry of the protein attachment to the solid surface, in order to minimize perturbation of the fluorescence sensing mechanism. Such constructs fuse an N- or C-terminal protein domain that can mediate site-specific attachment to an appropriately chemically activated surface. For instance, hexa-histidine peptide for metal-mediated immobilization, a hexa-lysine peptide for attachment to amine-reactive groups, or a zinc-finger domain (ZF-QNK) (Smith et al. 2005 Protein Sci, 14, 64-73), or a disulfide-containing truncated zinc finger (βZif) (Smith et al. 2005 Protein Sci, 14, 64-73) at N- or C-termini of the FRS to thiol-reactive groups (FIG. 13). Here we show that site-specific attachment of a robust glucose sensor to suitably derivatized agarose beads conserves its emission fluorescence spectral response, binding affinity, and thermostability.

The ttGGBP182C.2.0⋅Acrylodan protein was site-specifically immobilized through its C-terminal hexa-histidine tag on commercially available magnetic beads coated with Ni-NTA. The use of magnetic beads affords a straightforward means for holding the beads in place within their respective sensor patches in the sampling cartridge with a magnetic field. Site-specific immobilization minimizes perturbation of the sensing mechanism. Comparison of protein thermostabilities determined in solution and on beads shows that protein is stability is not perturbed by immobilization (FIG. 14A-F) These glucose-responsive magnetic beads also useful to measure highly precise glucose titration curves (FIG. 15). Similarly, hexa-lysine fusion domains were immobilized on agarose beads derivatized with N-hydroxysuccinimide, and the QNK- or βZif-fusion on iodacetyl-derivatized beads. These fusion proteins also maintained their spectral, glucose affinities, and thermostabilities (FIG. 14D-F).

The glucose-responsive magnetic beads were dried by incubation at 50° C. for 20 minutes, using an aqueous ammonium bicarbonate buffer. The stability properties of the sensor were recovered completely upon rehydration (FIG. 14c ). The dried beads were aged in situ inside fully assembled sample-handling cartridges by incubation for up to 7 days at 25° C., ³⁷° C., and 50° C. in the dark. Fluorescence and glucose-responsive properties were tested in cartridges stored for 1, 2 and 7 days. At all temperatures, the fluorescence ratio in the absence of glucose, and the glucose affinities remained unchanged within the error of the observation. Therefore, a significant advantage of ttGGBP-based FRSs is that they are sufficiently robust to be handled at ambient temperatures in a desiccated state, greatly simplifying manufacturing, distribution, and long-term storage conditions.

EXAMPLE 9 Fluorescence Mechanism

The most effective glucose-sensing FRSs identified are based on singly labeled Acrylodan and Badan conjugates. These two dyes, and their parent, Prodan(Weber 1979 Biochemistry, 18, 3075-3078), belong to a class of fluorophores that can undergo internal rotations which change the electronic structures of excited state dipoles(Rettig 1986 Angew. Chem. Int. Ed. Engl., 25, 971-988; Grabowski et al. 2003 Chem Rev, 103, 3899-4032). The X-ray structure of Prodan shows that in the absence of external factors, the dimethyl amino (DMA) and carbonyl groups are coplanar with the naphthalene core, and the system is maximally conjugated. However, the DMA or carbonyl groups can twist out of plane, diminishing the extent of conjugation within the system, and increasing the degree of polarization of these groups. This enhanced polarization increases the magnitude of the excited state dipole, and correspondingly its sensitivity to the polarity of its surroundings, which manifests itself as general solvatochromic effects and responses to specific hydrogen-bonding interactions. There has been considerable debate regarding the magnitude of the dipole in the polarized state in Prodan (Weber 1979 Biochemistry, 18, 3075-3078; Balter 1988 Chem. Phys. Lett., 143, 565-570; Catalan 1991 Journal of Fluorescence, 1, 215-223; Nemkovich 2007 Journal of Photochemistry and Photobiology A: Chemistry, 185, 26-31; Samanta 2000 Journal of Physical Chemistry, 104, 8972-8975; Kawski 2001 Zeitschrift fur Naturforschung, 56a, 407-411; Kawski 2002 Zeitschrift fur Naturforschung, 57a, 716-722), whether the molecule undergoes twisting in the excited state, and if so, whether the carbonyl or the DMA groups twist (Nowak 1986 Journal of Molecular Structure, 139, 13-23; Heisel 1987 Chemical Physics Letters, 138, 321-326; Parusel 1997 J. Molec. Struct., 398, 341-346; Parusel 1998b Journal of Physical Chemistry, 102, 7149-7156; Parusel 1998a J. Chem. Soc., Faraday Trans., 94, 2923-2927; Mennucci 2008 Journal of Physical Chemistry, 112, 414-423; Adhikary 2009 Journal of Physical Chemistry, 113, 11999-12004; Marini 2010 Journal of Physical Chemistry, 114, 17128-17135; Pederzoli 2014 Chemical Physics Letters, 597, 57-62; Cwiklik 2011 J. Phys. Chem., 115, 11428-11437; Fukuda 2012 Chem. Phys. Lett., 552, 53-57; Barucha-Kraszewska 2010 Biochim Biophys Acta, 1798, 1724-1734; Nitschke 2012 J. Phys. Chem., 116, 2713-2721). A series of derivatives in which the DMA (Lobo 2003 Journal of Physical Chemistry, 107, 10938-10943; Davis 2005 J. Phys. Chem., 109, 1295-1298) or carbonyl (Everett 2010 Journal of Physical Chemistry, 114, 4946-4950) groups are held in planar or out-of-plane conformations have shown that it is twisting of the carbonyl and not the DMA group that alters Prodan polarization.

The collection of Acrylodan and Badan conjugates of mutant ecGGBP and ttGGBPs constructed and described herein contains several semi-synthetic glucose sensors that exhibit wavelength-dependent changes in fluorescence emission intensity in response to glucose binding. The best responses were observed for conjugates attached to ttGGBP F17C (SEQ ID NO: 51) and ttGGBP W182C (SEQ ID NO: 61) cysteines endosteric mutants that replace residues which form van der Waals contacts with the pyranose glucose ring. Remarkably, the emission intensity maxima shift in opposite directions at these two positions: glucose binding evinces a bathochromic shift for ttGGBP W182C and ecGGBP W183C Acrylodan conjugates, whereas at ttGGBP F17C and ecGGBP F16C both Acrylodan and Badan exhibit hypsochromic responses. Analysis of their ligand-mediated changes in the populations of excited state and ground state electronic transitions in combination with the X-ray structures of three different conjugates has enabled us to describe a mechanism for the fluorescence response to glucose binding.

Analysis of the emission intensity (FIGS. 16-18, Tables 7 and 8) and absorption spectra (FIG. 19) indicated that glucose binding alters the populations of two dominant electronic transitions in both the excited (S₁ and S₂) and ground (G₁ and G₂) states. In hypsochromic responses, the dominant excited state electronic transition shifts from S₁ (green) in the apo-protein, to S₂ (blue) in the glucose complex; in bathochromic responses, the opposite redistribution is observed, and the glucose complex is dominated by the S₁ (green) excited state. Similarly, in the ground state, hypsochromic responses shift the electronic transitions in the absorbance spectra from a low- (G₁) to a high-energy state (G₂); for bathochromic responses, the shift is G₂→G₁. Comparison of high-resolution X-ray structures of the ttGGBP F17C⋅Badan (hypsochromic response) and ttGGBP W182C⋅Acrylodan or ecGGBP W183C⋅Acrylodan (bathochromic responses) revealed that the fluorophore structures of the glucose complexes differ in these conjugates (FIGS. 9 and 10). From these observations we deduced that the G₁ ground state in ecGGBP W183C⋅Acrylodan corresponds to a planar fluorophore, whereas the G₂ state of F17C⋅Badan corresponds to twisted fluorophore carbonyl in which the carbonyl has repositioned out of the plane of the naphthalene ring.

These observations indicate that the changes in fluorescence intensities of glucose-responsive Acrylodan and Badan conjugates arise as a consequence of conformational coupling between ligand-mediated shifts in the population of protein conformations and internal twisting of the fluorophore carbonyl relative to its naphthalene ring. Like all periplasmic binding proteins, GGBP undergoes a large, ligand-mediated conformational change from an open to a closed state in which the ligand is enveloped between two domains that are linked by a flexible hinge. The protein conformations of the glucose complexes of the ttGGBP F17C⋅Badan, ttGGBP W182C⋅Acrylodan and ecGGBP W183C⋅Acrylodan conjugates are as closed as the unmodified, wild-type proteins. The fluorophores do not occupy the positions of the wild-type aromatic rings that they replace, but instead point outwards into the solvent such that their dimethylamino groups make no contacts with the protein and is coplanar with naphthalene ring (e.g., in the case of ttGGBP17C⋅Badan, where the structure of this group is unambiguous). By contrast, the carbonyl is located at the end of the linker through which the fluorophore is coupled to the protein cysteine. The torsion between it and the naphthalene ring therefore is affected by a combination of interactions with residues proximal to the attachment site and distal interactions with the ring. Ligand-mediated signaling occurs if two conditions are satisfied: (i) the protein interacts with both the naphthalene and the carbonyl, stabilizing their relative twist, and (ii) these interactions differ in the open and closed states.

Analysis of the spectra of all conjugates (Tables 7 and 8) showed that these signaling conditions are satisfied most commonly if the fluorophore is planar in the open, ligand-free protein conformation and twists in the closed conformation of the glucose complex. In the case of F17C⋅Badan structure, the closed protein conformation stabilizes the twisted form by interactions with both the carbonyl and the naphthalene ring. These interactions are contributed by distal residues in the domain located opposite the fluorophore attachment point, and therefore are likely to be present in the closed but not open protein conformation. Less commonly, the fluorophore twists in the open protein conformation through proximal interactions, and becomes untwisted in the closed conformation. The ttGGBP W182C⋅Acrylodan and ecGGBP W183C⋅Acrylodan conjugates represent this case. The interactions that stabilize the twisted state in the open protein conformation have not been identified, but the structure of the closed conformation reveals an absence of interactions that twist the naphthalene ring and carbonyl relative to each other and the fluorophore adopts a low-energy planar state.

Mutations that affect ligand binding (Table 6) also can influence spectroscopic properties (Table 8). In the Class 1 PCS mutant H151Q ratiometry is abolished, by diminishing the fraction of S₂ that forms in the glucose complex. In D15A the redistribution of the two excited populations enhances ratiometric responses in both conjugates. In Class 2 mutants, the intrinsic equilibrium between the open and closed conformations is manipulated. In all the Class 2 mutants of both F17C Acrylodan and Badan conjugates, the fraction of the S₁ state in the apo-protein (^(apo)f(S₁)) is altered. These effects can both enhance or abolish wavelength shifts (Table 7 and 8). For instance, shifts are strengthened in the mutant Badan conjugates, but abolished in the Acrylodan conjugates as evidenced by the magnitude of the C₂ component. Mutations in the carbonyl hole (Class 3a) and the fluorophore channel walls (Class 3b) have large effects on glucose binding and fluorescence spectra. Many of the N258 mutants in the carbonyl hole do not respond to glucose. The absence of shifts in thermal stability in the presence of glucose indicates that these mutants no longer bind ligand. The 17C⋅Acrylodan N258S mutant conjugate is the exception: it binds and responds to glucose, but binding does not alter the distribution of excited state populations. Mutations in residues located on either side of the channel wall strongly influence both the distributions of the excited states in the ligand-free protein, and their ligand-mediated redistribution. Mutations in A260 all switch the 17C⋅Badan conjugate from a mixture of S₁ and S₂ states in the apo-protein to a predominantly S₁ state that exhibit small redistributions in response to glucose. Accordingly, most mutant conjugates exhibit isochromic instead of hypsochromic responses to glucose, with exception of 17C⋅Badan A260W which retains (diminished) hypsochromicity. By contrast, the 17C⋅Acrylodan A260 mutants retain the mixed S₁ and S₂ population in the apo-protein, but all response to glucose binding.

Although conformational coupling between the open and closed forms of the protein and the fluorophore internal torsional equilibrium is a major factor in determining the ligand-responsive changes in fluorescence of the Acrylodan and Badan conjugates, environmental effects on excited state dipole strengths also contribute, as evidenced by the presence of fine structure in the residuals between the models and obervations (FIGS. 17 and 18). The conjugates or their mutants differ in the degree to which fine structure is present in the emission spectra and responsive to glucose. This fine structure is due to changes in the energies of the S₁ and S₂ excited states associated with differences of their local environment in the open and closed conformations. The analysis presented here treats these differences as an ensemble average approximation.

The mechanism described is consistent with observations of the experimental properties of Prodan derivatives in which the twisted state of either the DMA or the carbonyl groups were controlled by synthesis of conformationally constrained groups (Lobo 2003 Journal of Physical Chemistry, 107, 10938-10943; Davis 2005 J. Phys. Chem., 109, 1295-1298; Green 2012 J. Org. Chem., 78, 1784-1789; Everett 2010 Journal of Physical Chemistry, 114, 4946-4950; Naughton 2013 J. Phys. Chem., 117, 3323-3327; Nikitina 2013 J. Phys. Chem., 117, 9189-9195; Daneri 2015 Journal of Photochemistry and Photobiology A: Chemistry, 310, 106-112).

Semisynthetic, fluorescently responsive proteins are useful in the development of reagentless biosensors with a wide variety of applications. However, in the absence of design principles that guide choice and placement of fluorophores, systematic identification of suitable fluorescent conjugates remains a significant challenge in their construction. The mechanistic insights described herein have revealed three key aspects of the fluorescence signal transduction mechanism that enable, inform, and direct rational engineering of fluorescent responses:

-   -   1. Signaling is controlled by the twisting of the carbonyl         group, and changes in the specific interactions between it and         the protein matrix via ligand-mediated protein conformational         changes.     -   2. The linker length and concomitant degrees of torsional         freedom determine the effectiveness of the ligand-mediated         conformational coupling between the protein and the carbonyl at         a given attachment position.     -   3. The planar ring system which determines the wavelength         absorption and emission characteristics is not constrained by         the protein matrix, but points outwards into the solvent.

The first two observations enable and direct structure-based approaches for identifying attachment positions and optimizing the functionalized linker for covalent modification. In such approaches, the internal flexibility of the linker is modeled, and the resulting library of fluorophore conformations are placed in a three-dimensional model of a protein host, checked for steric compatibility with their environment, and attachment sites and possible additional mutations identified that (de)stabilize a particular conformation or hydrogen bond with the protein exclusively in the apo-protein or ligand complex. The third observation indicates that the feasibility of introducing alternative chromophore structures that alter the fluorescence characteristics of the basic Prodan framework, while maintaining ligand-responsive signaling, provided the structural characteristics of the carbonyl and linker are maintained. Of particular interest are the design and construction of chromophore variants with wavelengths in the transparent window of blood (>600 nm). These principles are applied not only to periplasmic binding proteins and Prodan derivatives, but also to establish conformational coupling of any suitably placed, internally twisting fluorophore in proteins that undergo ligand-mediated changes in protein conformations.

TABLE 1 PCS position and sequence # Accession code Species 14 16 91 152 1 2GBP (seed structure) Escherichia coli D F N H 2 NC_013654|YP_003350022.1 Escherichia coli D F N H 3 NC_016822|YP_005457115.1 Shigella sonnei D F N H 4 NC_017328|YP_005727882.1 Shigella flexneri D F N H 5 NC_011740|YP_002383354.1 Escherichia fergusonii D F N H 6 NC_010658|YP_001879517.1 Shigella boydii D F N H 7 NC_022912|Asd1617_02874 Shigella dysenteriae D F N H 8 NC_013716|YP_003365823.1 Citrobacter rodentium D F N H 9 NC_009792|YP_001452231.1 Citrobacter koseri D F N H 10 NC_021500|H650_06520 Enterobacter sp. D F N H 11 NC_014121|ECL_03459 Enterobacter cloacae D F N H 12 NC_015968|YP_004829427.1 Enterobacter asburiae D F N H 13 NC_009778|YP_001437192.1 Cronobacter sakazakii D F N H 14 NC_016514|YP_004952913.1 Enterobacter cloacae D F N H 15 NC_011283|YP_002237430.1 Klebsiella pneumoniae D F N H 16 NC_020063|YP_007339667.1 Enterobacteriaceae bacterium D F N H 17 NC_016810|YP_005182060.1 Salmonella enterica D F N H 18 NC_013850|YP_003438413.1 Klebsiella variicola D F N H 19 NC_013282|YP_003211183.1 Cronobacter turicensis D F N H 20 NC_021232|YP_007990486.1 Klebsiella pneumoniae D F N H 21 NC_015761|YP_004730836.1 Salmonella bongori D F N H 22 NC_016612|YP_005021097.1 Klebsiella oxytoca D F N H 23 NC_009436|YP_001177466.1 Enterobacter sp. D F N H 24 NC_011147|YP_002141464.1 Salmonella enterica D F N H 25 NC_021066|YP_007872566.1 Raoultella ornithinolytica D F N H 26 NC_015663|YP_004594960.1 Enterobacter aerogenes D F N H 27 NC_014618|YP_003941097.1 Enterobacter lignolyticus D F N H 28 NC_015224|YP_004297664.1 Yersinia enterocolitica D F N H 29 NC_020211|YP_007405370.1 Serratia marcescens D F N H 30 NC_021741|M495_07335 Serratia liguefaciens D F N H 31 NC_014029|YP_003567546.1 Yersinia pestis D F N H 32 NC_010634|YP_001872058.1 Yersinia pseudotuberculosis D F N H 33 NC_009832|YP_001477795.1 Serratia proteamaculans D F N H 34 NC_015567|YP_004504928.1 Serratia plymuthica D F N H 35 NC_015566|YP_004499976.1 Serratia sp. D F N H 36 NC_015061|YP_004212168.1 Rahnella sp. D F N H 37 NC_016818|YP_005199494.1 Rahnella aquatilis D F N H 38 NC_007712|YP_454643.1 Sodalis glossinidius D F N H 39 NC_020418|YP_007506508.1 Morganella morganii D F N H 40 NC_021290|YP_008045423.1 Aeromonas hydrophila D F N H 41 NC_012912|YP_003005296.1 Dickeya zeae D F N H 42 NC_014562|YP_003931657.1 Pantoea vagans D F N H 43 NC_014837|YP_004116494.1 Pantoea sp. D F N H 44 NC_014500|YP_003882024.1 Dickeya dadantii D F N H 45 NC_014306|YP_003742362.1 Erwinia billingiae D F N H 46 NC_015424|YP_004390764.1 Aeromonas veronii D F N H 47 NC_013956|YP_003520836.1 Pantoea ananatis D F N H 48 NC_022546|YP_008651638.1 Plautia stali D F N H 49 NC_009348|YP_001140155.1 Aeromonas salmonicida D F N H 50 NC_010694|YP_001907230.1 Erwinia tasmaniensis D F N H 51 NC_013961|YP_003531646.1 Erwinia amylovora D F N H 52 NC_022268|YP_008522161.1 Serratia sp. D F N H 53 NC_012691|YP_002893819.1 Tolumonas auensis D F N H 54 NC_006371|YP_133522.1 Photobacterium profundum D F N H 55 NC_020802|YP_007640992.1 Psychromonas sp. D F N H 56 NC_022223|N175_08855 Listonella anguillarum D F N H 57 NC_015633|YP_004566361.1 Vibrio anguillarum D F N H 58 NC_016445|YP_004936985.1 Vibrio cholerae D F N H 59 NC_016602|YP_004992976.1 Vibrio furnissii D F N H 60 NC_015460|YP_004420811.1 Gallibacterium anatis D F N H 61 NC_014966|YP_004190360.1 Vibrio vulnificus D F N H 62 NC_006300|YP_087835.1 Mannheimia succiniciproducens D F N H 63 NC_015964|YP_004822812.1 Haemophilus parainfluenzae D F N H 64 NC_012913|YP_003007706.1 Aggregatibacter aphrophilus D F N H 65 NC_000907|NP_438982.2 Haemophilus influenzae D F N H 66 NC_009655|YP_001345182.1 Actinobacillus succinogenes D F N H 67 NC_014920|YP_004135881.1 Haemophilus influenza D F N H 68 NC_016513|YP_004948894.1 Aggregatibacter actinomycetemc D F N H 69 NC_010939|YP_001969307.1 Actinobacillus pleuropneumonia D F N H 70 NC_016808|YP_005176051.1 Pasteurella multocida D F N H 71 NC_010519|YP_001783460.1 Haemophilus somnus D F N H 72 NC_021082|YP_007882660.1 Mannheimia haemolytica D F N H 73 NC_017846|YP_006287121.1 Aggregatibacter actinomycetemc D F N H 74 NC_018690|YP_006818133.1 Actinobacillus suis D F N H 75 NC_011852|YP_002475059.1 Haemophilus parasuis D F N H 76 NC_008312|YP_720691.1 Trichodesmium erythraeum D F N H 77 NC_020515|YP_007548075.1 Bibersteinia trehalosi D F N H 78 NC_022524|N288_24375 Bacillus infantis D F N H 79 NC_021281|YP_008019649.1 Fusobacterium nucleatum D F N H 80 NC_003454|NP_604062.1 Fusobacterium nucleatum D F N H 81 NC_003366|NP_562257.1 Clostridium perfringens D F N H 82 NC_018607|YP_006708369.1 Brachyspira pilosicoli D F N H 83 NC_019908|YP_007234804.1 Brachyspira pilosicoli D F N H 84 NC_012225|YP_002722709.1 Brachyspira hyodysenteriae D F N H 85 NC_017243|YP_005593986.1 Brachyspira intermedia D F N H 86 NC_014150|YP_003634598.1 Brachyspira murdochii D F N H 87 NC_014330|YP_003786208.1 Brachyspira pilosicoli D F N H 88 NC_012491|YP_002770161.1 Brevibacillus brevis D F N H 89 NC_015732|YP_004698509.1 Treponema caldaria D F N H 90 NC_020291|Cspa_c46680 Clostridium saccharoperbutylac D F N H 91 NC_009617|YP_001311499.1 Clostridium beijerinckii D F N H 92 NC_014364|YP_003802961.1 Spirochaeta smaragdinae D Y N H 93 NC_015152|YP_004246106.1 Sphaerochaeta globosa D F N H 94 NC_014392|YP_003839461.1 Caldicellulosiruptor obsidians D F N H 95 NC_015578|YP_004532181.1 Treponema primitia D F N H 96 NC_014410|YP_003852930.1 Thermoanaerobacterium thermosa D F N H 97 NC_012914|YP_003010600.1 Paenibacillus sp. D F N H 98 NC_010278|YP_001651502.1 Actinobacillus pleuropneumonia D F N H 99 NC_016633|YP_005062659.1 Sphaerochaeta pleomorpha D F N H 100 NC_014393|YP_003845273.1 Clostridium cellulovorans D F N H 101 NC_014652|YP_003991244.1 Caldicellulosiruptor hydrother D F N H 102 NC_022777|YP_008772951.1 Clostridium tetani D F N H 103 NC_018690|YP_006817320.1 Actinobacillus suis D F N H 104 NC_009053|YP_001053159.1 Actinobacillus pleuropneumonia D F N H 105 NC_014393|YP_003845272.1 Clostridium cellulovorans D F N N 106 NC_010939|YP_001968321.1 Actinobacillus pleuropneumonia D F N H 107 NC_021658|SCE1572_01005 Sorangium cellulosum N F N H 108 NC_015690|YP_004645360.1 Paenibacillus mucilaginosus D F N H 109 NC_016935|YP_005316341.1 Paenibacillus mucilaginosus D F N H 110 NC_012914|YP_003013039.1 Paenibacillus sp. D F N H 111 NC_015519|YP_004460241.1 Tepidanaerobacter acetatoxydan D F N H 112 NC_013406|YP_003243743.1 Paenibacillus sp. D F N H 113 NC_015519|YP_004461277.1 Tepidanaerobacter acetatoxydan D F N H 114 NC_013517|YP_003308491.1 Sebaldella termitidis D F N H 115 NC_014150|YP_003634599.1 Brachyspira murdochii D F N H 116 NC_015436|YP_004411990.1 Sphaerochaeta coccoides D F N H 117 NC_021038|YP_007827124.1 Fretibacterium fastidiosum D F N H 118 NC_020291|Cspa_c46620 Clostridium saccharoperbutylac D F N H 119 NC_009617|YP_001311493.1 Clostridium beijerinckii D F N H 120 NC_015977|YP_004837837.1 Roseburia hominis D F N H 121 NC_021018|YP_007796707.1 Coprococcus sp. D F N H 122 NC_021042|YP_007838599.1 Faecalibacterium prausnitzii D F N N 123 NC_012781|YP_002936409.1 Eubacterium rectale D F N H 124 NC_015601|YP_004561181.1 Erysipelothrix rhusiopathiae D F N N 125 NC_021354|YP_008073256.1 Erysipelothrix rhusiopathiae D F N N 126 NC_021012|YP_007778124.1 Roseburia intestinalis D F N H 127 NC_022592|CAETHG_2989 Clostridium autoethanogenum N W N N 128 NC_014328|CLIU_c08950 Clostridium ljungdahlii N W N N 129 NC_021020|YP_007799070.1 Faecalibacterium prausnitzii D F N N 130 NC_021040|YP_007833443.1 Roseburia intestinalis D F N H 131 NC_021035|YP_007824422.1 butyrate-producing bacterium D F N N 132 NC_021012|YP_007778116.1 Roseburia intestinalis D F N N 133 NC_015977|YP_004837830.1 Roseburia hominis D F N N 134 NC_021040|YP_007833436.1 Roseburia intestinalis D F N N 135 NC_014376|YP_003822569.1 Clostridium saccharolyticum D F N N 136 NC_022549|YP_008656214.1 Acholeplasma brassicae D F N H 137 NC_014387|YP_003830205.1 Butyrivibrio proteoclasticus D F N N 138 NC_014376|YP_003822565.1 Clostridium saccharolyticum D F N N PCS position and sequence # 154 158 183 211 236 256 Identity Thermophilicity Gram 1 D R W N D N 2 D R W N D N 1.00 Mesophilic − 3 D R W N D N 1.00 Mesophilic − 4 D R W N D N 1.00 Mesophilic − 5 D R W N D N 1.00 Mesophilic − 6 D R W N D N 1.00 Mesophilic − 7 D R W N D N 1.00 Mesophilic − 8 D R W N D N 0.97 Mesophilic − 9 D R W N D N 0.96 Mesophilic − 10 D R W N D N 0.95 Mesophilic − 11 D R W N D N 0.95 Mesophilic − 12 D R W N D N 0.95 Mesophilic − 13 D R W N D N 0.94 Mesophilic − 14 D R W N D N 0.94 Mesophilic − 15 D R W N D N 0.94 Mesophilic − 16 D R W N D N 0.94 Mesophilic + 17 D R W N D N 0.94 Mesophilic − 18 D R W N D N 0.94 Mesophilic − 19 D R W N D N 0.94 Mesophilic − 20 D R W N D N 0.94 Mesophilic − 21 D R W N D N 0.94 Mesophilic − 22 D R W N D N 0.94 Mesophilic − 23 D R W N D N 0.94 Mesophilic − 24 D R W N D N 0.94 Mesophilic − 25 D R W N D N 0.93 Mesophilic + 26 D R W N D N 0.93 Mesophilic − 27 D R W N D N 0.93 Mesophilic − 28 D R W N D N 0.90 Mesophilic − 29 D R W N D N 0.88 Mesophilic + 30 D R W N D N 0.88 Mesophilic + 31 D R W N D N 0.87 Mesophilic − 32 D R W N D N 0.87 Mesophilic − 33 D R W N D N 0.87 Mesophilic + 34 D R W N D N 0.86 Mesophilic + 35 D R W N D N 0.86 ? + 36 D R W N D N 0.86 Mesophilic + 37 D R W N D N 0.85 Mesophilic + 38 D R W N D N 0.84 Mesophilic − 39 D R W N D N 0.82 Mesophilic + 40 D R W N D N 0.82 Mesophilic − 41 D R W N D N 0.82 Mesophilic − 42 D R W N D N 0.81 Mesophilic − 43 D R W N D N 0.81 Mesophilic − 44 D R W N D N 0.81 Mesophilic − 45 D R W N D N 0.81 Mesophilic − 46 D R W N D N 0.81 Mesophilic − 47 D R W N D N 0.81 Mesophilic − 48 D R W N D N 0.80 Mesophilic + 49 D R W N D N 0.80 Mesophilic − 50 D R W N D N 0.80 Mesophilic − 51 D R W N D N 0.79 Mesophilic − 52 D R W N D N 0.78 ? + 53 D R W N D N 0.76 Mesophilic − 54 D R W N D N 0.74 Psychrophilic − 55 D R W N D N 0.72 Mesophilic + 56 D R W N D N 0.72 Mesophilic + 57 D R W N D N 0.72 Mesophilic − 58 D R W N D N 0.72 Mesophilic − 59 D R W N D N 0.71 Mesophilic − 60 D R W N D N 0.71 Mesophilic − 61 D R W N D N 0.71 Mesophilic − 62 D R W N D N 0.70 Mesophilic + 63 D R W N D N 0.70 Mesophilic − 64 D R W N D N 0.69 Mesophilic − 65 D R W N D N 0.69 Mesophilic − 66 D R W N D N 0.69 Mesophilic − 67 D R W N D N 0.69 Mesophilic − 68 D R W N D N 0.68 Mesophilic − 69 D R W N D N 0.68 Mesophilic − 70 D R W N D N 0.68 Mesophilic − 71 D R W N D N 0.68 Mesophilic − 72 D R W N D N 0.68 Mesophilic + 73 D R W N D N 0.68 Mesophilic − 74 D R W N D N 0.67 Mesophilic − 75 D R W N D N 0.66 Mesophilic − 76 D R W N D N 0.59 Mesophilic − 77 D R W N D N 0.58 Mesophilic + 78 D R W N D N 0.58 Mesophilic + 79 D R W N D N 0.58 Mesophilic − 80 D R W N D N 0.57 Mesophilic − 81 D R W N D N 0.56 Mesophilic + 82 D R W N D N 0.53 Mesophilic − 83 D R W N D N 0.52 Mesophilic − 84 D R W N D N 0.52 Mesophilic − 85 D R W N D N 0.52 ? − 86 D R W N D N 0.52 Mesophilic − 87 D R W N D N 0.51 Mesophilic − 88 D R W N D N 0.50 Mesophilic + 89 D R W N D N 0.50 Mesophilic − 90 D R W N D N 0.49 Mesophilic + 91 D R W N D N 0.49 Mesophilic + 92 D R W N D N 0.49 Mesophilic − 93 D R W N D N 0.48 Mesophilic + 94 D R W N D N 0.48 Hyperthermophilic + 95 D R W N D N 0.48 Mesophilic − 96 D R W N D N 0.48 Thermophilic + 97 D R W N D N 0.48 Mesophilic + 98 D R W N D N 0.48 Mesophilic − 99 D R W N D N 0.48 Mesophilic + 100 D R W N D N 0.47 Mesophilic + 101 D R W N D N 0.47 Hyperthermophilic + 102 D R W N D N 0.47 Mesophilic + 103 D R W N D N 0.47 Mesophilic − 104 D R W N D N 0.47 Mesophilic − 105 D R W N D N 0.47 Mesophilic + 106 D R W N D N 0.46 Mesophilic − 107 D R W N D N 0.46 Mesophilic − 108 D R W N D N 0.46 Mesophilic + 109 D R W N D N 0.45 Mesophilic + 110 D R W N D N 0.44 Mesophilic + 111 D R W N D N 0.44 Mesophilic + 112 D R W N D N 0.44 Mesophilic + 113 D R W N D N 0.43 Mesophilic + 114 D R W N D N 0.43 Mesophilic − 115 D R W N D N 0.43 Mesophilic − 116 D R W N D N 0.41 Mesophilic + 117 D R W N D N 0.41 Mesophilic + 118 D R W N D N 0.40 Mesophilic + 119 D R W N D N 0.39 Mesophilic + 120 D R W N D N 0.38 Mesophilic + 121 D R W N D N 0.38 Mesophilic + 122 D R W N D N 0.37 Mesophilic − 123 D R W N D N 0.37 Mesophilic + 124 D R W N D N 0.36 Mesophilic + 125 D R W N D N 0.36 Mesophilic + 126 D R W N D N 0.36 Mesophilic + 127 D R W N D N 0.36 Mesophilic + 128 D R W N D N 0.35 Mesophilic + 129 D R W N D N 0.34 Mesophilic − 130 D R W N D N 0.34 Mesophilic + 131 D R W N D N 0.33 Mesophilic ? 132 D R W N D N 0.33 Mesophilic + 133 D R W N D N 0.33 Mesophilic + 134 D R W N D N 0.32 Mesophilic + 135 D R W N D N 0.31 Mesophilic + 136 D R W N D N 0.31 Mesophilic + 137 D R W N D N 0.30 Mesophilic + 138 D R W N D N 0.29 Mesophilic + Each nucleotide and amino acid sequence associated with the accession numbers listed in Table 1 is hereby incorporated by reference in its entirety.

TABLE 2 Glucose-binding properties of E. coli GGBP SAFE sequence homologs. T_(m) shift with Percent Accession number Protein name Expression^(a) Glucose^(a) Identity NC_013654|YP_003350022.1 ecGGBP Y Y 100 NC_014376|YP_003822565.1 csaGGBP Y Y 29 NC_014387|YP_003830205.1 bprGGBP N 30 NC_021012|YP_007778116.1 rinGGBP_A N 33 NC_021020|YP_007799070.1 fprGGBP Y Y 34 NC_014328|CLJU_c08950 cljGGBP N 35 NC_022592|CAETHG_2989 cauGGBP N 36 NC_021012|YP_007778124.1 rinGGBP_B Y Y 36 NC_015601|YP_004561181.1 erhGGBP Y Y 36 NC_012781|YP_002936409.1 ereGGBP N 37 NC_014410|YP_003852930.1 ttGGBP Y Y 48 NC_014392|YP_003839461.1 cobGGBP Y Too 48 thermostable^(b) NC_014652|YP_003991244.1 chyGGBP Y Too 47 thermostable^(b) NC_013406|YP_003243743.1 pspGGBP N 44 ^(a)Y, Yes; N, No. ^(b)Determined using fluorescent Acrylodan conjugates (see text).

TABLE 3 Glucose response of Acrylodan and Badan conjugates in a cysteine scan of the ttGGBP scaffold. Emission K_(d) ^(d,e) ^(apo)T_(m) Wavelength (nm) (mM) Mutation Class^(a) Shape^(b) Conjugate^(c) (K) λ1 λ2 ^(app)K_(d) ^(true)K_(d) Y11C p m A 351 511 470 0.12 0.16 d B 349 492 528 0.28 0.24 T16C p m A 351 519 460 8.8  12    m B 349 — — nb nb F17C e d A 349 482 542 0.08 0.06 d B 346 467 491  0.087 0.26 N42C p A 350 — — nb nb B 324 — — nb nb V67C p A 350 — — nb nb B 322 — — nb nb R91C e m A 349 491 540 0.18 0.17 B 348 — —  nb^(d)  nb^(d) E92C p A 350 — — nb nb B 346 — — nb nb A111C p m A 350 515 550  0.19^(d)  0.11^(d) m/d B 348 523 550 0.64 0.55 Q148C p A 351 — — nb nb B 349 — — nb nb H151C e m A 351 511 489  0.012  0.025 m B 348 523 550   0.018^(d)   0.027^(d) Q152C p A 351 — —  nb^(d)  nb^(d) B 349 — — nb nb N181C p A 350 — — nb nb B 349 — — nb nb W182C e d A 347 479 526 2.3  2.3  m B 347 515 550 27    19    D183C p A 348 — —  nb^(d)  nb^(d) B 348 — — nb nb L257C a A 352 — — nb nb B 348 — — nb nb D259C a A 349 — — nb nb B 347 — — nb nb K300C a A 349 — — nb nb B 348 — — nb nb ^(a)a, allosteric; e, endosteric; p, peristeric. ^(b)m, monochromatic; d, dichromatic (i.e. spectral shape change). ^(c)A, Acrylodan; B, Badan. ^(d)noisy data and or bad fit. ^(e)nb; no binding, nd; not determined.

TABLE 4 Responses of fluorophores conjugated to F17C and W182C mutants of ttGGBP^(a). λ_(ex) ^(apo)λ_(max) ^(apo)I_(max) ^(sat)λ_(max) ^(sat)I_(max) ^(true)K_(d) Position Fluorophore^(b) (nm)^(c) (nm) (AU ×1000) (nm) (AU ×1000) (mM)  17C Acrylodan 391 487 15.9 487 20.0 0.2 Badan 391 519 12.8 467 52.6 0.1 5-IAF 491 523 64.3 523 70.6 61.3 Oregon green 496 523 101.9 523 91.7 — CPM 384 471 78.5 467 90.9 17.0 IANBD 478 531 15.3 535 19.8 11.8 IAEDANS 336 467 12.5 467 14.4 — Pacific Blue 410 451 28.6 455 108.6 60.7 182C Acrylodan 391 479 55.0 515 17.2 6.0 Badan 391 515 16.8 515 11.9 64.9 5-IAF 491 519 255.0 519 453.2 5.0 6-IAF 491 513 50.4 513 63.1 750 Oregon green 496 519 78.2 519 186.2 20.0 CPM 384 479 49.5 483 40.3 6.8 IANBD 478 543 29.1 547 12.5 210 IAEDANS 336 487 3.7 483 7.9 0.2 Pacific Blue 410 455 115.0 455 119.4 — BODIPY 499 499 519 40.1 515 80.2 30.7 BODIPY 507 507 531 32.9 535 31.4 11.0 Alexa 488 495 519 211.6 519 182.2 — Alexa 532 532 551 63.0 551 61.0 — Alexa 546 546 571 152.1 571 150.2 — Texas Red 595 611 23.3 611 23.5 — Cy 5 646 663 19.2 663 23.3 210 PyPMPO 415 555 3.7 559 4.2 20.6 ^(a)λ_(ex), preferred excitation wavelength (from supplier); ^(apo)λ_(max), observed maximum emission wavelength of the apo-protein; ^(apo)I_(max), observed intensity at ^(apo)λ_(max); ^(apo)λ_(max), observed maximum emission wavelength of the glucose complex; ^(sat)I_(max), observed intensity at ^(sat)λ_(max); ^(true)K_(d), affinity determined from fit of equation 1 to the monochromatic emission intensities. Emission spectra were measured on the Nanodrop3300, using ~10 μM protein. The observed absolute emission intensities are a rough guide to the brightness of the conjugate, because the protein concentration was approximately the same for each experiment. ^(b)Abbreviations, chemical names and supplier catalogue numbers as follows: Acrylodan (A433); Badan (B6057); 5-IAF (I30451); Oregon Green 488 (O6034); CPM (D346); IANBD (D2004); IAEDANS (I14); Pacific Blue (P30506); BODIPY 499 (D20350); BODIPY 507 (D6004); BODIPY 577 (D20351); Alexa 532 (A10255); Alexa 555 (A20346); Texas Red (T6008); PyMPO (M6026) from Life Technologies and Cy5 (13080) from Lumiprobe. ^(c)The Nanodrop3300 fixed wavelength LED that most closely matched λ_(ex) was used (see Materials and Methods).

TABLE 5 Crystallographic data collection and refinement statistics.^(a) ttGGBP17C- ttGGBP182C.2.0- ecGGBP183C- Badan Acrylodan Acrylodan X-ray source 22-ID, SER- 22-ID, SER- 22-BM, SER- CAT, APS CAT, APS CAT, APS Wavelength (Å) 1.0 1.0 1.0 Space Group P2₁2₁2₁ P2₁2₁2₁ C121 Unit Cell parameters (Å) a, b, c 45.49, 53.06, 45.67, 53.17, 119.58, 36.53, 134.32 133.57 79.90 90.00 (α), 124.13 (β), 90.00 (γ) Resolution range (Å) 41.63-1.59 (1.62-1.59) 33.70-1.39 50.00-1.53 (1.56-1.53) Completeness (%) 99.8 (99.3) 98.9 (94.9) 98.8 (94.6) No. of unique reflections 44590     65108 (9969) 43030     Wilson B-factor (Å²) 15.50 11.50 12.60 Multiplicity 7.21 (7.22) 5.29 (5.17) 6.5 (5.1) R-sym (%) 0.08 (0.69) 0.08 (0.76) 0.06 (0.29) R-pim (%) 0.03 (0.25) 0.04 (0.34) 0.025 (0.131) Mean I/σ (I) 16.40 (3.58) 13.71 (2.87) 25.54 (3.99) Refinement statistics R factor (%) 15.11 15.88 15.04 Free_R_factor (%) 17.07 17.74 16.75 Average B-factor (Å2) 20.10 17.90 18.60 Macromolecules 17.70 15.30 15.90 Water 34.30 34.10 34.60 Glucose/Fluorophore 9.50/39.90 8.60/39.10 22.70/64.50 Number of non-hydrogen atoms Macromolecule 2471    2493    2358    Glucose 24^(b  ) 24^(b  ) 72^(c  ) Calcium 1   1   1   Fluorophore 16   17   17   Water 407    391    325    RMS deviations RMS (bonds)  0.007  0.005  0.006 RMS (angles)  1.112  0.822  1.060 Ramachandran favoured (%) 97.81 98.44 98.71 Ramachandran allowed (%)  1.88  1.25  0.97 Ramachandran outliers (%)  0.31  0.31  0.32 Rotamer outliers (%)  0.00  0.00  0.00 Clashscore  1.60  0.79  1.03 ^(a)Values for highest resolution shell are given in parentheses. ^(b)Two conformations. ^(c)Five molecules.

TABLE 6 Responses of mutant HGGBP17C and ttGGBP182C conjugates^(a). Emission Glucose^(d) Galactose^(d) ^(apo)T_(m) wavelength (nm) ^(app)K_(d) ^(true)K_(d) ^(true)K_(d) Protein Mutation Class^(b) Conjugate^(c) (K) λ1 λ2 (mM) (mM) (mM) S ttGBP17C B 346 467 519 0.10 0.15  0.19 1.3 ″ A 349 487 515 0.08 0.09 3.8 43 ttGGBP17C.1 R91K, Q148E 2 B 463 515 0.6 0.8 0.4 0.46 ttGGBP17C.2 R69P, Q152P 2 B 350 479 523 8.6 10.8 5.2 0.48 ″ ″ 2 A 492 515 15 18 5.0 0.28 ttGGBP17C.3 T16N, D211A 2 B 346 471 531 3.4 4.1 2.5 0.61 ″ ″ 2 A 495 529 1.4 1.5  0.53 0.35 ttGGBP17C.4 H151Q 1 B 347 511 457 16 6.4 14   2.2 ″ ″ 1 A 488 550 50 48 14   0.29 ttGGBP17C.5 D15A 1 B 345 487 530 16 16 4.2 0.26 ″ ″ 1 A 348 483 498 6 6 2.4 0.41 ttGGBP17C.6 D15E 1 B 346 467 525 3.3 3.6  3.6^(e) 1 ttGGBP17C.7 D15N 1 B 347 483 515 0.75 1.0  0.64 0.64 ″ ″ 1 A 348 483 515 0.3 0.3 0.3 0.91 ttGGBP17C.8 T16N 2 A 348 487 529 0.61 0.60  0.26 0.43 ttGGBP17C.9 T16S 2 A 487 520 0.2 0.20 nd ttGGBP17C.10 G20A 3 A 351 487 520 0.4 0.4 nd ttGGBP17C.11 T240A 3 A 348 487 500 0.04 0.04 nd ttGGBP17C.19 N258D 3 B 344 nb^(e) nb^(e) nb^(e) ttGGBP17C.20 N258S 3 B 344 nb^(e) nb^(e) nb^(e) ttGGBP17C.21 N258A 3 B 345 532 494 61 69 nb  ttGGBP17C.22 A260N 3 B 343 523 492 12 15 530^(e)   ttGGBP17C.23 A260Q 3 B 344 527 490 15 18 nb^(c) ttGGBP17C.24 A260R 3 B 344 490 515 1.8 1.7 29   17 ttGGBP17C.25 A260K 3 B 515 493 3.2 3.7 nb^(e) ttGGBP17C.26 A260W 3 B 346 523 509 0.9 0.9 14   16 ttGGBP17C.27 A260F 3 B 346 523 490 0.2 0.3 8.8 33 ttGGBP17C.28 A260Y 3 B 346 523 494 0.06 0.07 2.6 37 ttGGBP17C.29 A260S 3 B 343 527 496 2.1 2.2 250    114 ttGGBP182C A 347 472 535 2.2 2.3 3.3 1.4 ttGGBP182C.2.0^(f) R91K Q148E 2, 3 A 346 475 545 4.5 6.0 18.5  3.1 ttGGBP182C.2.1^(g) A154S 1 A 328 480 552 3.0 4.1 13.1  3.2 ttGGBP182C.2.3^(g) A154N 1 A 346 470 537 16.3 19.0 207    10.9 ttGGBP182C.2.4^(g) A154M 1 A 346 472 540 0.4 0.4 4.5 11.2 ttGGBP182C.2.5^(g) H151Q 1 A 346 477 542 10.8 13.0 20.3  1.6 ttGGBP182C.2.6^(g) H151N 1 A 347 475 537 19.2 17.9 52.6  2.9 ttGGBP182C.2.7^(g) H151F 1 A 346 475 545 121 124 ttGGBP182C.2.8^(g) D15N 1 A 343 474 542 179 209 372    1.8 ttGGBP182C.2.9^(g) A154F 1 A 345 512 477 0.4 0.3 1.6 4.0 ttGGBP182C.3^(f) R91K 2 A 346 494 459 1.8 0.9 3.1 3.4 ttGGBP182C.4^(f) Q148E 2 A 347 475 542 0.6 0.8 6.5 8.1 ttGGBP182C.5^(f) R69P Q152P 2 A 349 477 535 7.5 8.8 7.4 0.8 ttGGBP182C.6^(f) T16N D211A 2 A 345 472 530 21.6 27.6 81   2.9 ttGGBP182C.7^(f) R91K Q148S 2, 3 A 346 478 550 0.3 0.4 1.1 3.7 ttGGBP182C.8^(f) R91K Q148K 2, 3 A 346 475 545 28.7 44.2 256    5.8 ttGGBP182C.9^(f) D15N 1 A 343 475 540 75.1 76.4 282    3.7 ^(a)Measured on the Nanodrop at room temperature. λ_(max) is the wavelength corresponding to the maximum emission intensity. Optimal ratiometry wavelengths are determined according to the analysis described in Materials and Methods (equation 7). The ^(true)K_(d) is determined from monochromatic titration curves; ^(app)K_(d) from dichromatic ratiometry (equations 5 and 6). Average relative error in the ^(true)K_(d) values is 5%, in the ^(app)K_(d) values, 1%. S is the selectivity between glucose and galactose, S = ^(true)K_(d)(galactose)/^(true)K_(d)(glucose); S > 1, selective for glucose. ^(b)1, PCS; 2, inter-domain interaction; 3, contact between protein and fluorophore ^(c)A, Acrylodan; B, Badan. ^(d)nb, no bonding; nd, not determined. ^(e)Noisy data or bad fit. ^(f)Additional mutation constructed in ttGGBP182C. ^(g)Additional mutation constructed in ttGGBP182C.2.0.

TABLE 7 Spectral analysis of ttGGBP and ecGGBP Acrylodan and Badan conjugates^(a). SVD component Gaussians Muta- fractions Peaks (nm) Fraction f(S₁) tion Conjugate^(b) C₁ C₂ S₁ S₂ Apo Sat Y11C A r (h) 0.97 0.03 515 463 1.00 0.88 B r (h) 0.84 0.16 532 484 1.00 0.47 T16C A n — — 518 — 1.00 — B n — — 539 446 0.96 — F17C A r (h) 0.90 0.09 527 486 0.56 0.16 B r (h) 0.89 0.10 535 474 0.66 0.15 F16C A r (h) 0.91 0.08 509 454 0.63 0.10 (Ec) B r (h) 0.92 0.06 522 469 0.56 0.14 N42C A n — — 518 — 1.00 — B n — — 516 — 1.00 — V67C A n — — 522 464 0.59 — B n — — 523 480 0.38 — R91C A i 0.97 0.02 533 488 0.43 0.92 B n — — 522 476 0.51 — E92C A n — — 520 — 1.00 — B n — — 522 — 1.00 — A111C A d 0.98 0.01 520 474 0.98 0.95 B d 0.98 0.02 529 467 0.91 0.84 Q148C A n — — 537 491 0.26 — B n — — 576 519 0.15 — H151C A i 0.97 0.02 520 490 1.00 0.86 B i 0.98 0.01 533 477 0.98 1.00 Q152C A n — — 520 — 1.00 — B n — — 524 472 0.74 — N181C A n — — 527 — 1.00 — B n — — 545 — 1.00 — W182C A r (b) 0.87 0.13 500 463 0.63 0.99 B d 0.98 0.02 521 479 0.91 1.00 W183C A r (b) 0.84 0.15 527 481 0.37 0.81 (Ec) D183C A d 523 — 1.00 — B n — — 530 477 0.61 — L257C A n — — 533 496 0.29 — B n — — 516 — 1.00 — D259C A n — — 516 — 1.00 — B n — — 521 — 1.00 — K300C A n — — 520 — 1.00 — B n — — 528 — 1.00 — ^(a)Emission spectra determined on Nanodrop3300. SVD analysis according to equations 11-13. Gaussian fits according to equations 14-15. ^(b)A, Acrylodan; B, Badan; n, no observed response to glucose; r (h), ratiometric (hypsochromic shift); r (b), ratiometric (bathochromic shift); i, intensity increase only; d, intensity decrease only.

TABLE 8 Spectral analysis of ttGGBP.17C Acrylodan and Badan conjugates^(a). SVD component Gaussians fractions Peaks (nm) Fraction f(S₁) Protein Mutation Conjugate^(b) C₁ C₂ S₁ S₂ Apo Sat ttGGBP17C.1 R91K, Q148E A d 0.95 0.04 518 490 0.71 0.60 ″ ″ B r(h) 0.85 0.14 532 472 0.64 0.15 ttGGBP17C.2 R69P, Q152P A d 0.92 0.06 528 462 0.88 0.73 ″ ″ B r(h) 0.86 0.13 542 476 0.64 0.36 ttGGBP17C.3 T16N, D211A A d 0.94 0.05 519 458 0.83 0.70 ″ ″ B r(h) 0.81 0.18 540 474 0.70 0.30 ttGGBP17C.8 T16N A r(h) 0.93 0.07 533 496 0.30 0.00 ttGGBP17C.9 T16S A r(h) 0.94 0.06 510 488 1.00 0.43 ttGGBP17C.4 H151Q A r(h) 0.95 0.04 526 485 0.65 0.52 ″ ″ B r(h) 0.95 0.04 540 486 0.50 0.39 ttGGBP17C.5 D15A A r(h) 0.87 0.13 491 465 0.98 0.22 ″ ″ B r(h) 0.84 0.15 525 470 0.58 0.16 ttGGBP17C.6 D15E A n — — 511 448 0.72 — ″ ″ B r(h) 0.90 0.09 525 473 0.39 0.15 ttGGBP17C.7 D15N A d 0.97 0.02 492 464 0.86 1.00 ″ ″ B d 0.92 0.05 533 480 0.22 0.16 ttGGBP17C.19 N258D A n — — 525 475 0.30 — ″ ″ B n — — 523 — 1.00 — ttGGBP17C.20 N258S A d 0.99 0.00 530 479 0.37 0.36 ″ ″ B n — — 524 — 1.00 — ttGGBP17C.21 N258A A n — — 526 475 0.33 — ″ ″ B n — — 523 — 1.00 — ttGGBP17C.10 G20A A d 0.95 0.04 534 487 0.28 0.21 ttGGBP17C.11 T240A A d 0.95 0.03 541 487 0.35 0.25 ttGGBP17C.22 A260N A n — — 528 475 0.33 — ″ ″ B i 0.97 0.03 531 480 0.96 0.85 ttGGBP17C.23 A260Q A i — — 526 474 0.31 — ″ ″ B i 0.97 0.03 532 475 0.95 0.85 ttGGBP17C.24 A260R A n — — 525 474 0.26 — ″ ″ B i 0.96 0.03 523 483 0.90 0.75 ttGGBP17C.25 A260K A n — — 526 473 0.24 — ″ ″ B i 0.96 0.03 519 482 0.90 0.76 ttGGBP17C.26 A260W A i 0.99 0.01 530 479 0.42 0.41 ″ ″ B r(h) 0.96 0.04 529 478 1.00 0.87 ttGGBP17C.27 A260F A n — — 523 477 0.38 — ″ ″ B i 0.96 0.04 529 487 1.00 0.82 ttGGBP17C.28 A260Y A n — — 523 477 0.38 — ″ ″ B i 0.97 0.03 530 480 1.00 0.87 ttGGBP17C.29 A260S A n — — 526 474 0.32 — ″ ″ B i 0.96 0.03 533 478 0.95 0.83 ^(a)Emission spectra determined on Nanodrop3300. SVD analysis according to equations 11-13. Gaussian fits according to equations 14-15. ^(b)A, Acrylodan; B, Badan; n, no observed response to glucose; r(h), ratiometric (hypsochromic shift); r(b), ratiometric (bathochromic shift); i, intensity increase only; d, intensity decrease only.

EXAMPLE 10 Crystal Structure Coordinates for an E. coli Glucose-Galactose Binding Protein: ECGGBP183C (Acrylodan Attached to W183C Mutant)

Naming is standard three-letter amino acid code.

Atom positions are provided as Cartesian coordinates, using standard Protein Databank (PDB) format. ATOM records refer to amino acid atoms; HETATM records refer to non-amino acid atoms.

Column 1: record type (ATOM or HETATM); column 2: atom number; column 3 atom name (standard naming scheme for amino acids); column 4: residue name (ATOM records), or component name (HETATM records); column 5: chain identifier (A, B, C, . . . ); column 6: amino acid residue sequence number (ATOM records), or component number (HETATM records); columns 7-9: x,y,z atomic Cartesian positional coordinates; column 10: fractional occupancy (set to 1.0 in this listing); column 11: B-factor (ignored in this listing); column 12: file identifier (ignored in this listing); column 13: line number (same as atom number in this listing).

For heteroatom (HETATM) records, the component name (column 4) is as follows:

CA, calcium

HOH, water

ACR, Acrylodan

K, potassium

EDO, ethylene glycol

ATOM 1 O ALA A 2 106.533 −15.459 75.201 1.00 0.00 xxxx 1 ATOM 2 N ALA A 2 107.059 −18.172 74.462 1.00 0.00 xxxx 2 ATOM 3 CA ALA A 2 105.803 −17.753 75.070 1.00 0.00 xxxx 3 ATOM 4 C ALA A 2 105.616 −16.243 74.951 1.00 0.00 xxxx 4 ATOM 5 CB ALA A 2 105.744 −18.181 76.527 1.00 0.00 xxxx 5 ATOM 6 N THR A 3 104.414 −15.847 74.566 1.00 0.00 xxxx 6 ATOM 7 CA THR A 3 104.079 −14.441 74.397 1.00 0.00 xxxx 7 ATOM 8 C THR A 3 103.547 −13.847 75.689 1.00 0.00 xxxx 8 ATOM 9 O THR A 3 102.489 −14.249 76.156 1.00 0.00 xxxx 9 ATOM 10 CB THR A 3 103.023 −14.268 73.301 1.00 0.00 xxxx 10 ATOM 11 OG1 THR A 3 103.556 −14.752 72.060 1.00 0.00 xxxx 11 ATOM 12 CG2 THR A 3 102.616 −12.817 73.168 1.00 0.00 xxxx 12 ATOM 13 N ARG A 4 104.268 −12.892 76.272 1.00 0.00 xxxx 13 ATOM 14 CA ARG A 4 103.781 −12.274 77.501 1.00 0.00 xxxx 14 ATOM 15 C ARG A 4 102.892 −11.082 77.169 1.00 0.00 xxxx 15 ATOM 16 O ARG A 4 103.286 −10.224 76.378 1.00 0.00 xxxx 16 ATOM 17 CB ARG A 4 104.947 −11.827 78.392 1.00 0.00 xxxx 17 ATOM 18 CG ARG A 4 105.839 −12.971 78.910 1.00 0.00 xxxx 18 ATOM 19 CD ARG A 4 106.999 −12.408 79.742 1.00 0.00 xxxx 19 ATOM 20 NE ARG A 4 107.840 −13.464 80.300 1.00 0.00 xxxx 20 ATOM 21 CZ ARG A 4 108.891 −13.259 81.091 1.00 0.00 xxxx 21 ATOM 22 NH1 ARG A 4 109.247 −12.027 81.435 1.00 0.00 xxxx 22 ATOM 23 NH2 ARG A 4 109.589 −14.293 81.541 1.00 0.00 xxxx 23 ATOM 24 N ILE A 5 101.699 −11.040 77.760 1.00 0.00 xxxx 24 ATOM 25 CA ILE A 5 100.798 −9.892 77.638 1.00 0.00 xxxx 25 ATOM 26 C ILE A 5 100.536 −9.303 79.016 1.00 0.00 xxxx 26 ATOM 27 O ILE A 5 100.148 −10.025 79.938 1.00 0.00 xxxx 27 ATOM 28 CB ILE A 5 99.484 −10.290 76.931 1.00 0.00 xxxx 28 ATOM 29 CG2 ILE A 5 98.491 −9.115 76.932 1.00 0.00 xxxx 29 ATOM 30 CG1 ILE A 5 99.787 −10.790 75.514 1.00 0.00 xxxx 30 ATOM 31 CD1 ILE A 5 98.552 −11.286 74.772 1.00 0.00 xxxx 31 ATOM 32 N GLY A 6 100.775 −8.001 79.158 1.00 0.00 xxxx 32 ATOM 33 CA GLY A 6 100.613 −7.324 80.436 1.00 0.00 xxxx 33 ATOM 34 C GLY A 6 99.242 −6.689 80.534 1.00 0.00 xxxx 34 ATOM 35 O GLY A 6 98.785 −6.074 79.579 1.00 0.00 xxxx 35 ATOM 36 N VAL A 7 98.583 −6.847 81.678 1.00 0.00 xxxx 36 ATOM 37 CA VAL A 7 97.232 −6.313 81.871 1.00 0.00 xxxx 37 ATOM 38 C VAL A 7 97.186 −5.551 83.186 1.00 0.00 xxxx 38 ATOM 39 O VAL A 7 97.627 −6.074 84.212 1.00 0.00 xxxx 39 ATOM 40 CB VAL A 7 96.160 −7.449 81.885 1.00 0.00 xxxx 40 ATOM 41 CG1 VAL A 7 94.781 −6.891 82.114 1.00 0.00 xxxx 41 ATOM 42 CG2 VAL A 7 96.199 −8.257 80.605 1.00 0.00 xxxx 42 ATOM 43 N THR A 8 96.645 −4.333 83.183 1.00 0.00 xxxx 43 ATOM 44 CA THR A 8 96.381 −3.648 84.448 1.00 0.00 xxxx 44 ATOM 45 C THR A 8 94.872 −3.426 84.569 1.00 0.00 xxxx 45 ATOM 46 O THR A 8 94.217 −2.977 83.620 1.00 0.00 xxxx 46 ATOM 47 CB THR A 8 97.147 −2.294 84.570 1.00 0.00 xxxx 47 ATOM 48 OG1 THR A 8 96.693 −1.384 83.556 1.00 0.00 xxxx 48 ATOM 49 CG2 THR A 8 98.676 −2.510 84.446 1.00 0.00 xxxx 49 ATOM 50 N ILE A 9 94.335 −3.761 85.739 1.00 0.00 xxxx 50 ATOM 51 CA ILE A 9 92.933 −3.546 86.095 1.00 0.00 xxxx 51 ATOM 52 C ILE A 9 92.893 −2.377 87.059 1.00 0.00 xxxx 52 ATOM 53 O ILE A 9 93.694 −2.340 87.986 1.00 0.00 xxxx 53 ATOM 54 CB ILE A 9 92.334 −4.809 86.743 1.00 0.00 xxxx 54 ATOM 55 CG1 ILE A 9 92.474 −6.004 85.801 1.00 0.00 xxxx 55 ATOM 56 CG2 ILE A 9 90.886 −4.563 87.149 1.00 0.00 xxxx 56 ATOM 57 CD1 ILE A 9 91.634 −5.899 84.523 1.00 0.00 xxxx 57 ATOM 58 N TYR A 10 91.994 −1.411 86.871 1.00 0.00 xxxx 58 ATOM 59 CA TYR A 10 92.119 −0.166 87.630 1.00 0.00 xxxx 59 ATOM 60 C TYR A 10 91.894 −0.426 89.119 1.00 0.00 xxxx 60 ATOM 61 O TYR A 10 92.540 0.190 89.952 1.00 0.00 xxxx 61 ATOM 62 CB TYR A 10 91.159 0.920 87.078 1.00 0.00 xxxx 62 ATOM 63 CG TYR A 10 89.811 1.015 87.771 1.00 0.00 xxxx 63 ATOM 64 CD1 TYR A 10 89.599 1.932 88.799 1.00 0.00 xxxx 64 ATOM 65 CD2 TYR A 10 88.745 0.201 87.388 1.00 0.00 xxxx 65 ATOM 66 CE1 TYR A 10 88.382 2.034 89.441 1.00 0.00 xxxx 66 ATOM 67 CE2 TYR A 10 87.514 0.286 88.034 1.00 0.00 xxxx 67 ATOM 68 CZ TYR A 10 87.340 1.210 89.055 1.00 0.00 xxxx 68 ATOM 69 OH TYR A 10 86.139 1.297 89.724 1.00 0.00 xxxx 69 ATOM 70 N LYS A 11 91.014 −1.375 89.430 1.00 0.00 xxxx 70 ATOM 71 CA LYS A 11 90.672 −1.735 90.799 1.00 0.00 xxxx 71 ATOM 72 C LYS A 11 90.059 −3.128 90.779 1.00 0.00 xxxx 72 ATOM 73 O LYS A 11 88.993 −3.327 90.195 1.00 0.00 xxxx 73 ATOM 74 CB LYS A 11 89.705 −0.687 91.376 1.00 0.00 xxxx 74 ATOM 75 CG LYS A 11 88.958 −1.080 92.621 1.00 0.00 xxxx 75 ATOM 76 CD LYS A 11 88.090 0.094 93.073 1.00 0.00 xxxx 76 ATOM 77 CE LYS A 11 87.341 −0.224 94.359 1.00 0.00 xxxx 77 ATOM 78 NZ LYS A 11 88.210 −0.910 95.353 1.00 0.00 xxxx 78 ATOM 79 N TYR A 12 90.728 −4.107 91.389 1.00 0.00 xxxx 79 ATOM 80 CA TYR A 12 90.288 −5.500 91.239 1.00 0.00 xxxx 80 ATOM 81 C TYR A 12 88.895 −5.769 91.789 1.00 0.00 xxxx 81 ATOM 82 O TYR A 12 88.194 −6.643 91.273 1.00 0.00 xxxx 82 ATOM 83 CB TYR A 12 91.252 −6.472 91.934 1.00 0.00 xxxx 83 ATOM 84 CG TYR A 12 92.199 −7.239 91.032 1.00 0.00 xxxx 84 ATOM 85 CD1 TYR A 12 92.817 −6.627 89.945 1.00 0.00 xxxx 85 ATOM 86 CD2 TYR A 12 92.527 −8.558 91.317 1.00 0.00 xxxx 86 ATOM 87 CE1 TYR A 12 93.724 −7.315 89.146 1.00 0.00 xxxx 87 ATOM 88 CE2 TYR A 12 93.421 −9.258 90.532 1.00 0.00 xxxx 88 ATOM 89 CZ TYR A 12 94.012 −8.626 89.443 1.00 0.00 xxxx 89 ATOM 90 OH TYR A 12 94.917 −9.315 88.675 1.00 0.00 xxxx 90 ATOM 91 N ASP A 13 88.491 −5.051 92.831 1.00 0.00 xxxx 91 ATOM 92 CA ASP A 13 87.206 −5.393 93.433 1.00 0.00 xxxx 92 ATOM 93 C ASP A 13 86.059 −4.494 92.973 1.00 0.00 xxxx 93 ATOM 94 O ASP A 13 84.973 −4.560 93.535 1.00 0.00 xxxx 94 ATOM 95 CB ASP A 13 87.311 −5.409 94.960 1.00 0.00 xxxx 95 ATOM 96 CG ASP A 13 87.822 −4.115 95.535 1.00 0.00 xxxx 96 ATOM 97 OD1 ASP A 13 88.328 −3.272 94.778 1.00 0.00 xxxx 97 ATOM 98 OD2 ASP A 13 87.738 −3.962 96.775 1.00 0.00 xxxx 98 ATOM 99 N ASP A 14 86.279 −3.693 91.933 1.00 0.00 xxxx 99 ATOM 100 CA ASP A 14 85.161 −3.118 91.169 1.00 0.00 xxxx 100 ATOM 101 C ASP A 14 84.313 −4.302 90.691 1.00 0.00 xxxx 101 ATOM 102 O ASP A 14 84.858 −5.221 90.091 1.00 0.00 xxxx 102 ATOM 103 CB ASP A 14 85.698 −2.279 90.001 1.00 0.00 xxxx 103 ATOM 104 CG ASP A 14 84.601 −1.711 89.124 1.00 0.00 xxxx 104 ATOM 105 OD1 ASP A 14 84.259 −0.523 89.295 1.00 0.00 xxxx 105 ATOM 106 OD2 ASP A 14 84.090 −2.449 88.260 1.00 0.00 xxxx 106 ATOM 107 N ASN A 15 83.007 −4.316 90.980 1.00 0.00 xxxx 107 ATOM 108 CA ASN A 15 82.192 −5.510 90.688 1.00 0.00 xxxx 108 ATOM 109 C ASN A 15 82.248 −5.882 89.215 1.00 0.00 xxxx 109 ATOM 110 O ASN A 15 82.458 −7.045 88.857 1.00 0.00 xxxx 110 ATOM 111 CB ASN A 15 80.724 −5.312 91.091 1.00 0.00 xxxx 111 ATOM 112 CG ASN A 15 80.549 −5.010 92.562 1.00 0.00 xxxx 112 ATOM 113 OD1 ASN A 15 81.029 −3.996 93.054 1.00 0.00 xxxx 113 ATOM 114 ND2 ASN A 15 79.794 −5.859 93.257 1.00 0.00 xxxx 114 ATOM 115 N PHE A 16 82.069 −4.897 88.348 1.00 0.00 xxxx 115 ATOM 116 CA PHE A 16 82.097 −5.199 86.927 1.00 0.00 xxxx 116 ATOM 117 C PHE A 16 83.483 −5.634 86.450 1.00 0.00 xxxx 117 ATOM 118 O PHE A 16 83.621 −6.611 85.693 1.00 0.00 xxxx 118 ATOM 119 CB PHE A 16 81.629 −3.995 86.120 1.00 0.00 xxxx 119 ATOM 120 CG PHE A 16 81.657 −4.235 84.646 1.00 0.00 xxxx 120 ATOM 121 CD1 PHE A 16 80.744 −5.096 84.058 1.00 0.00 xxxx 121 ATOM 122 CD2 PHE A 16 82.608 −3.621 83.856 1.00 0.00 xxxx 122 ATOM 123 CE1 PHE A 16 80.778 −5.335 82.689 1.00 0.00 xxxx 123 ATOM 124 CE2 PHE A 16 82.649 −3.859 82.482 1.00 0.00 xxxx 124 ATOM 125 CZ PHE A 16 81.731 −4.720 81.909 1.00 0.00 xxxx 125 ATOM 126 N MET A 17 84.521 −4.922 86.876 1.00 0.00 xxxx 126 ATOM 127 CA MET A 17 85.854 −5.278 86.404 1.00 0.00 xxxx 127 ATOM 128 C MET A 17 86.328 −6.622 86.968 1.00 0.00 xxxx 128 ATOM 129 O MET A 17 87.231 −7.255 86.403 1.00 0.00 xxxx 129 ATOM 130 CB MET A 17 86.862 −4.169 86.715 1.00 0.00 xxxx 130 ATOM 131 CG MET A 17 86.681 −2.912 85.854 1.00 0.00 xxxx 131 ATOM 132 SD MET A 17 86.502 −3.231 84.091 1.00 0.00 xxxx 132 ATOM 133 CE MET A 17 88.089 −3.976 83.741 1.00 0.00 xxxx 133 ATOM 134 N SER A 18 85.738 −7.047 88.082 1.00 0.00 xxxx 134 ATOM 135 CA SER A 18 85.999 −8.383 88.605 1.00 0.00 xxxx 135 ATOM 136 C SER A 18 85.524 −9.424 87.590 1.00 0.00 xxxx 136 ATOM 137 O SER A 18 86.219 −10.411 87.320 1.00 0.00 xxxx 137 ATOM 138 CB SER A 18 85.309 −8.577 89.957 1.00 0.00 xxxx 138 ATOM 139 OG SER A 18 85.592 −9.854 90.498 1.00 0.00 xxxx 139 ATOM 140 N VAL A 19 84.352 −9.186 87.004 1.00 0.00 xxxx 140 ATOM 141 CA VAL A 19 83.817 −10.081 85.982 1.00 0.00 xxxx 141 ATOM 142 C VAL A 19 84.735 −10.048 84.754 1.00 0.00 xxxx 142 ATOM 143 O VAL A 19 85.083 −11.091 84.201 1.00 0.00 xxxx 143 ATOM 144 CB VAL A 19 82.362 −9.716 85.597 1.00 0.00 xxxx 144 ATOM 145 CG1 VAL A 19 81.813 −10.737 84.609 1.00 0.00 xxxx 145 ATOM 146 CG2 VAL A 19 81.465 −9.656 86.832 1.00 0.00 xxxx 146 ATOM 147 N VAL A 20 85.130 −8.851 84.331 1.00 0.00 xxxx 147 ATOM 148 CA VAL A 20 85.985 −8.708 83.147 1.00 0.00 xxxx 148 ATOM 149 C VAL A 20 87.335 −9.385 83.329 1.00 0.00 xxxx 149 ATOM 150 O VAL A 20 87.796 −10.106 82.434 1.00 0.00 xxxx 150 ATOM 151 CB VAL A 20 86.174 −7.219 82.781 1.00 0.00 xxxx 151 ATOM 152 CG1 VAL A 20 87.190 −7.051 81.650 1.00 0.00 xxxx 152 ATOM 153 CG2 VAL A 20 84.842 −6.607 82.385 1.00 0.00 xxxx 153 ATOM 154 N ARG A 21 87.983 −9.163 84.468 1.00 0.00 xxxx 154 ATOM 155 CA ARG A 21 89.339 −9.679 84.636 1.00 0.00 xxxx 155 ATOM 156 C ARG A 21 89.329 −11.196 84.697 1.00 0.00 xxxx 156 ATOM 157 O ARG A 21 90.244 −11.850 84.184 1.00 0.00 xxxx 157 ATOM 158 CB ARG A 21 90.007 −9.074 85.875 1.00 0.00 xxxx 158 ATOM 159 CG ARG A 21 89.441 −9.508 87.206 1.00 0.00 xxxx 159 ATOM 160 CD ARG A 21 90.137 −8.696 88.303 1.00 0.00 xxxx 160 ATOM 161 NE ARG A 21 89.427 −8.720 89.582 1.00 0.00 xxxx 161 ATOM 162 CZ ARG A 21 89.481 −9.725 90.450 1.00 0.00 xxxx 162 ATOM 163 NH1 ARG A 21 90.195 −10.809 90.165 1.00 0.00 xxxx 163 ATOM 164 NH2 ARG A 21 88.817 −9.652 91.599 1.00 0.00 xxxx 164 ATOM 165 N LYS A 22 88.279 −11.766 85.280 1.00 0.00 xxxx 165 ATOM 166 CA LYS A 22 88.183 −13.214 85.344 1.00 0.00 xxxx 166 ATOM 167 C LYS A 22 87.954 −13.790 83.955 1.00 0.00 xxxx 167 ATOM 168 O LYS A 22 88.479 −14.857 83.616 1.00 0.00 xxxx 168 ATOM 169 CB LYS A 22 87.079 −13.628 86.315 1.00 0.00 xxxx 169 ATOM 170 CG LYS A 22 87.475 −13.286 87.751 1.00 0.00 xxxx 170 ATOM 171 CD LYS A 22 86.396 −13.653 88.756 1.00 0.00 xxxx 171 ATOM 172 CE LYS A 22 86.756 −13.110 90.132 1.00 0.00 xxxx 172 ATOM 173 NZ LYS A 22 85.780 −13.518 91.180 1.00 0.00 xxxx 173 ATOM 174 N ALA A 23 87.209 −13.060 83.132 1.00 0.00 xxxx 174 ATOM 175 CA ALA A 23 86.967 −13.508 81.769 1.00 0.00 xxxx 175 ATOM 176 C ALA A 23 88.242 −13.417 80.920 1.00 0.00 xxxx 176 ATOM 177 O ALA A 23 88.526 −14.326 80.142 1.00 0.00 xxxx 177 ATOM 178 CB ALA A 23 85.836 −12.705 81.144 1.00 0.00 xxxx 178 ATOM 179 N ILE A 24 89.023 −12.349 81.084 1.00 0.00 xxxx 179 ATOM 180 CA ILE A 24 90.285 −12.217 80.348 1.00 0.00 xxxx 180 ATOM 181 C ILE A 24 91.210 −13.367 80.728 1.00 0.00 xxxx 181 ATOM 182 O ILE A 24 91.874 −13.963 79.873 1.00 0.00 xxxx 182 ATOM 183 CB ILE A 24 90.973 −10.856 80.630 1.00 0.00 xxxx 183 ATOM 184 CG1 ILE A 24 90.144 −9.700 80.088 1.00 0.00 xxxx 184 ATOM 185 CD1 ILE A 24 90.752 −8.339 80.389 1.00 0.00 xxxx 185 ATOM 186 CG2 ILE A 24 92.403 −10.829 80.060 1.00 0.00 xxxx 186 ATOM 187 N GLU A 25 91.258 −13.684 82.019 1.00 0.00 xxxx 187 ATOM 188 CA GLU A 25 92.092 −14.790 82.474 1.00 0.00 xxxx 188 ATOM 189 C GLU A 25 91.698 −16.104 81.797 1.00 0.00 xxxx 189 ATOM 190 O GLU A 25 92.564 −16.883 81.400 1.00 0.00 xxxx 190 ATOM 191 CB GLU A 25 92.012 −14.942 83.990 1.00 0.00 xxxx 191 ATOM 192 CG GLU A 25 93.068 −15.883 84.537 1.00 0.00 xxxx 192 ATOM 193 CD GLU A 25 92.979 −16.034 86.033 1.00 0.00 xxxx 193 ATOM 194 OE1 GLU A 25 92.080 −16.763 86.503 1.00 0.00 xxxx 194 ATOM 195 OE2 GLU A 25 93.794 −15.401 86.738 1.00 0.00 xxxx 195 ATOM 196 N GLN A 26 90.399 −16.344 81.657 1.00 0.00 xxxx 196 ATOM 197 CA GLN A 26 89.935 −17.567 81.007 1.00 0.00 xxxx 197 ATOM 198 C GLN A 26 90.310 −17.606 79.525 1.00 0.00 xxxx 198 ATOM 199 O GLN A 26 90.686 −18.654 79.004 1.00 0.00 xxxx 199 ATOM 200 CB GLN A 26 88.425 −17.719 81.176 1.00 0.00 xxxx 200 ATOM 201 CG GLN A 26 88.009 −17.965 82.613 1.00 0.00 xxxx 201 ATOM 202 CD GLN A 26 88.675 −19.193 83.206 1.00 0.00 xxxx 202 ATOM 203 OE1 GLN A 26 89.258 −19.136 84.288 1.00 0.00 xxxx 203 ATOM 204 NE2 GLN A 26 88.589 −20.314 82.497 1.00 0.00 xxxx 204 ATOM 205 N ASP A 27 90.225 −16.464 78.850 1.00 0.00 xxxx 205 ATOM 206 CA ASP A 27 90.642 −16.386 77.454 1.00 0.00 xxxx 206 ATOM 207 C ASP A 27 92.129 −16.674 77.293 1.00 0.00 xxxx 207 ATOM 208 O ASP A 27 92.544 −17.394 76.367 1.00 0.00 xxxx 208 ATOM 209 CB ASP A 27 90.318 −15.009 76.874 1.00 0.00 xxxx 209 ATOM 210 CG ASP A 27 88.819 −14.753 76.777 1.00 0.00 xxxx 210 ATOM 211 OD1 ASP A 27 88.073 −15.718 76.515 1.00 0.00 xxxx 211 ATOM 212 OD2 ASP A 27 88.386 −13.591 76.968 1.00 0.00 xxxx 212 ATOM 213 N ALA A 28 92.941 −16.146 78.202 1.00 0.00 xxxx 213 ATOM 214 CA ALA A 28 94.386 −16.360 78.126 1.00 0.00 xxxx 214 ATOM 215 C ALA A 28 94.736 −17.813 78.417 1.00 0.00 xxxx 215 ATOM 216 O ALA A 28 95.608 −18.381 77.762 1.00 0.00 xxxx 216 ATOM 217 CB ALA A 28 95.123 −15.427 79.088 1.00 0.00 xxxx 217 ATOM 218 N LYS A 29 94.047 −18.412 79.388 1.00 0.00 xxxx 218 ATOM 219 CA LYS A 29 94.249 −19.820 79.742 1.00 0.00 xxxx 219 ATOM 220 C LYS A 29 94.004 −20.738 78.556 1.00 0.00 xxxx 220 ATOM 221 O LYS A 29 94.648 −21.784 78.416 1.00 0.00 xxxx 221 ATOM 222 CB LYS A 29 93.326 −20.223 80.895 1.00 0.00 xxxx 222 ATOM 223 CG LYS A 29 93.781 −19.726 82.256 1.00 0.00 xxxx 223 ATOM 224 CD LYS A 29 92.810 −20.153 83.347 1.00 0.00 xxxx 224 ATOM 225 CE LYS A 29 93.250 −19.641 84.712 1.00 0.00 xxxx 225 ATOM 226 NZ LYS A 29 94.578 −20.190 85.114 1.00 0.00 xxxx 226 ATOM 227 N ALA A 30 93.067 −20.343 77.703 1.00 0.00 xxxx 227 ATOM 228 CA ALA A 30 92.696 −21.144 76.544 1.00 0.00 xxxx 228 ATOM 229 C ALA A 30 93.770 −21.106 75.461 1.00 0.00 xxxx 229 ATOM 230 O ALA A 30 93.772 −21.936 74.549 1.00 0.00 xxxx 230 ATOM 231 CB ALA A 30 91.364 −20.665 75.982 1.00 0.00 xxxx 231 ATOM 232 N ALA A 31 94.675 −20.137 75.562 1.00 0.00 xxxx 232 ATOM 233 CA ALA A 31 95.722 −19.923 74.566 1.00 0.00 xxxx 233 ATOM 234 C ALA A 31 97.061 −20.427 75.093 1.00 0.00 xxxx 234 ATOM 235 O ALA A 31 97.695 −19.760 75.905 1.00 0.00 xxxx 235 ATOM 236 CB ALA A 31 95.813 −18.437 74.210 1.00 0.00 xxxx 236 ATOM 237 N PRO A 32 97.511 −21.593 74.622 1.00 0.00 xxxx 237 ATOM 238 CA PRO A 32 98.679 −22.204 75.270 1.00 0.00 xxxx 238 ATOM 239 C PRO A 32 99.986 −21.419 75.097 1.00 0.00 xxxx 239 ATOM 240 O PRO A 32 100.924 −21.659 75.859 1.00 0.00 xxxx 240 ATOM 241 CB PRO A 32 98.775 −23.576 74.592 1.00 0.00 xxxx 241 ATOM 242 CG PRO A 32 98.064 −23.417 73.288 1.00 0.00 xxxx 242 ATOM 243 CD PRO A 32 96.963 −22.433 73.545 1.00 0.00 xxxx 243 ATOM 244 N ASP A 33 100.043 −20.498 74.139 1.00 0.00 xxxx 244 ATOM 245 CA ASP A 33 101.282 −19.774 73.856 1.00 0.00 xxxx 245 ATOM 246 C ASP A 33 101.348 −18.412 74.543 1.00 0.00 xxxx 246 ATOM 247 O ASP A 33 102.256 −17.629 74.271 1.00 0.00 xxxx 247 ATOM 248 CB ASP A 33 101.469 −19.593 72.345 1.00 0.00 xxxx 248 ATOM 249 CG ASP A 33 100.328 −18.833 71.692 1.00 0.00 xxxx 249 ATOM 250 OD1 ASP A 33 99.197 −18.858 72.222 1.00 0.00 xxxx 250 ATOM 251 OD2 ASP A 33 100.564 −18.214 70.629 1.00 0.00 xxxx 251 ATOM 252 N VAL A 34 100.404 −18.145 75.442 1.00 0.00 xxxx 252 ATOM 253 CA VAL A 34 100.292 −16.842 76.101 1.00 0.00 xxxx 253 ATOM 254 C VAL A 34 100.593 −16.957 77.589 1.00 0.00 xxxx 254 ATOM 255 O VAL A 34 100.154 −17.901 78.247 1.00 0.00 xxxx 255 ATOM 256 CB VAL A 34 98.890 −16.238 75.893 1.00 0.00 xxxx 256 ATOM 257 CG1 VAL A 34 98.702 −14.981 76.733 1.00 0.00 xxxx 257 ATOM 258 CG2 VAL A 34 98.670 −15.936 74.435 1.00 0.00 xxxx 258 ATOM 259 N GLN A 35 101.361 −16.004 78.108 1.00 0.00 xxxx 259 ATOM 260 CA GLN A 35 101.497 −15.833 79.544 1.00 0.00 xxxx 260 ATOM 261 C GLN A 35 100.909 −14.485 79.915 1.00 0.00 xxxx 261 ATOM 262 O GLN A 35 101.363 −13.445 79.433 1.00 0.00 xxxx 262 ATOM 263 CB GLN A 35 102.946 −15.910 79.997 1.00 0.00 xxxx 263 ATOM 264 CG GLN A 35 103.098 −15.718 81.497 1.00 0.00 xxxx 264 ATOM 265 CD GLN A 35 104.544 −15.694 81.942 1.00 0.00 xxxx 265 ATOM 266 OE1 GLN A 35 105.461 −15.777 81.125 1.00 0.00 xxxx 266 ATOM 267 NE2 GLN A 35 104.757 −15.577 83.249 1.00 0.00 xxxx 267 ATOM 268 N LEU A 36 99.886 −14.513 80.755 1.00 0.00 xxxx 268 ATOM 269 CA LEU A 36 99.221 −13.304 81.202 1.00 0.00 xxxx 269 ATOM 270 C LEU A 36 99.905 −12.748 82.449 1.00 0.00 xxxx 270 ATOM 271 O LEU A 36 100.128 −13.494 83.396 1.00 0.00 xxxx 271 ATOM 272 CB LEU A 36 97.760 −13.610 81.499 1.00 0.00 xxxx 272 ATOM 273 CG LEU A 36 96.815 −12.427 81.600 1.00 0.00 xxxx 273 ATOM 274 CD1 LEU A 36 96.635 −11.829 80.218 1.00 0.00 xxxx 274 ATOM 275 CD2 LEU A 36 95.484 −12.898 82.173 1.00 0.00 xxxx 275 ATOM 276 N LEU A 37 100.264 −11.462 82.445 1.00 0.00 xxxx 276 ATOM 277 CA LEU A 37 100.825 −10.832 83.641 1.00 0.00 xxxx 277 ATOM 278 C LEU A 37 99.845 −9.749 84.060 1.00 0.00 xxxx 278 ATOM 279 O LEU A 37 99.835 −8.664 83.473 1.00 0.00 xxxx 279 ATOM 280 CB LEU A 37 102.215 −10.236 83.379 1.00 0.00 xxxx 280 ATOM 281 CG LEU A 37 103.399 −11.161 83.055 1.00 0.00 xxxx 281 ATOM 282 CD1 LEU A 37 103.232 −11.921 81.751 1.00 0.00 xxxx 282 ATOM 283 CD2 LEU A 37 104.663 −10.338 82.976 1.00 0.00 xxxx 283 ATOM 284 N MET A 38 99.015 −10.023 85.063 1.00 0.00 xxxx 284 ATOM 285 CA MET A 38 97.926 −9.095 85.382 1.00 0.00 xxxx 285 ATOM 286 C MET A 38 98.051 −8.491 86.779 1.00 0.00 xxxx 286 ATOM 287 O MET A 38 98.323 −9.194 87.751 1.00 0.00 xxxx 287 ATOM 288 CB MET A 38 96.567 −9.791 85.224 1.00 0.00 xxxx 288 ATOM 289 CG MET A 38 95.373 −8.825 85.176 1.00 0.00 xxxx 289 ATOM 290 SD MET A 38 93.881 −9.536 84.433 1.00 0.00 xxxx 290 ATOM 291 CE MET A 38 93.470 −10.772 85.662 1.00 0.00 xxxx 291 ATOM 292 N ASN A 39 97.827 −7.180 86.849 1.00 0.00 xxxx 292 ATOM 293 CA ASN A 39 98.037 −6.372 88.051 1.00 0.00 xxxx 293 ATOM 294 C ASN A 39 96.781 −5.654 88.498 1.00 0.00 xxxx 294 ATOM 295 O ASN A 39 95.965 −5.230 87.672 1.00 0.00 xxxx 295 ATOM 296 CB ASN A 39 99.110 −5.310 87.811 1.00 0.00 xxxx 296 ATOM 297 CG ASN A 39 100.506 −5.893 87.698 1.00 0.00 xxxx 297 ATOM 298 OD1 ASN A 39 101.171 −5.706 86.692 1.00 0.00 xxxx 298 ATOM 299 ND2 ASN A 39 100.961 −6.585 88.746 1.00 0.00 xxxx 299 ATOM 300 N ASP A 40 96.664 −5.511 89.812 1.00 0.00 xxxx 300 ATOM 301 CA ASP A 40 95.672 −4.650 90.460 1.00 0.00 xxxx 301 ATOM 302 C ASP A 40 96.287 −3.286 90.729 1.00 0.00 xxxx 302 ATOM 303 O ASP A 40 97.214 −3.168 91.537 1.00 0.00 xxxx 303 ATOM 304 CB ASP A 40 95.198 −5.300 91.771 1.00 0.00 xxxx 304 ATOM 305 CG ASP A 40 94.113 −4.502 92.473 1.00 0.00 xxxx 305 ATOM 306 OD1 ASP A 40 93.553 −3.564 91.862 1.00 0.00 xxxx 306 ATOM 307 OD2 ASP A 40 93.809 −4.848 93.635 1.00 0.00 xxxx 307 ATOM 308 N SER A 41 95.772 −2.247 90.076 1.00 0.00 xxxx 308 ATOM 309 CA SER A 41 96.320 −0.910 90.271 1.00 0.00 xxxx 309 ATOM 310 C SER A 41 95.785 −0.231 91.531 1.00 0.00 xxxx 310 ATOM 311 O SER A 41 96.189 0.875 91.841 1.00 0.00 xxxx 311 ATOM 312 CB SER A 41 96.033 −0.043 89.042 1.00 0.00 xxxx 312 ATOM 313 OG SER A 41 96.652 −0.624 87.893 1.00 0.00 xxxx 313 ATOM 314 N GLN A 42 94.886 −0.899 92.258 1.00 0.00 xxxx 314 ATOM 315 CA GLN A 42 94.410 −0.381 93.547 1.00 0.00 xxxx 315 ATOM 316 C GLN A 42 93.869 1.053 93.455 1.00 0.00 xxxx 316 ATOM 317 O GLN A 42 94.044 1.857 94.371 1.00 0.00 xxxx 317 ATOM 318 CB GLN A 42 95.537 −0.455 94.588 1.00 0.00 xxxx 318 ATOM 319 CG GLN A 42 96.023 −1.898 94.793 1.00 0.00 xxxx 319 ATOM 320 CD GLN A 42 96.973 −2.066 95.967 1.00 0.00 xxxx 320 ATOM 321 OE1 GLN A 42 97.611 −1.116 96.411 1.00 0.00 xxxx 321 ATOM 322 NE2 GLN A 42 97.071 −3.296 96.474 1.00 0.00 xxxx 322 ATOM 323 N ASN A 43 93.207 1.350 92.336 1.00 0.00 xxxx 323 ATOM 324 CA ASN A 43 92.564 2.646 92.099 1.00 0.00 xxxx 324 ATOM 325 C ASN A 43 93.531 3.835 92.253 1.00 0.00 xxxx 325 ATOM 326 O ASN A 43 93.151 4.906 92.726 1.00 0.00 xxxx 326 ATOM 327 CB ASN A 43 91.361 2.817 93.037 1.00 0.00 xxxx 327 ATOM 328 CG ASN A 43 90.360 3.824 92.517 1.00 0.00 xxxx 328 ATOM 329 OD1 ASN A 43 90.301 4.088 91.319 1.00 0.00 xxxx 329 ATOM 330 ND2 ASN A 43 89.572 4.405 93.423 1.00 0.00 xxxx 330 ATOM 331 N ASP A 44 94.777 3.646 91.829 1.00 0.00 xxxx 331 ATOM 332 CA ASP A 44 95.807 4.677 91.943 1.00 0.00 xxxx 332 ATOM 333 C ASP A 44 96.592 4.708 90.630 1.00 0.00 xxxx 333 ATOM 334 O ASP A 44 97.292 3.749 90.300 1.00 0.00 xxxx 334 ATOM 335 CB ASP A 44 96.709 4.362 93.149 1.00 0.00 xxxx 335 ATOM 336 CG ASP A 44 97.743 5.434 93.437 1.00 0.00 xxxx 336 ATOM 337 OD1 ASP A 44 98.249 6.082 92.510 1.00 0.00 xxxx 337 ATOM 338 OD2 ASP A 44 98.075 5.609 94.631 1.00 0.00 xxxx 338 ATOM 339 N GLN A 45 96.493 5.798 89.872 1.00 0.00 xxxx 339 ATOM 340 CA GLN A 45 97.187 5.839 88.587 1.00 0.00 xxxx 340 ATOM 341 C GLN A 45 98.708 5.795 88.731 1.00 0.00 xxxx 341 ATOM 342 O GLN A 45 99.393 5.237 87.860 1.00 0.00 xxxx 342 ATOM 343 CB GLN A 45 96.780 7.085 87.788 1.00 0.00 xxxx 343 ATOM 344 CG GLN A 45 97.318 7.082 86.362 1.00 0.00 xxxx 344 ATOM 345 CD GLN A 45 96.752 5.928 85.546 1.00 0.00 xxxx 345 ATOM 346 OE1 GLN A 45 95.544 5.714 85.521 1.00 0.00 xxxx 346 ATOM 347 NE2 GLN A 45 97.630 5.174 84.884 1.00 0.00 xxxx 347 ATOM 348 N SER A 46 99.237 6.372 89.811 1.00 0.00 xxxx 348 ATOM 349 CA SER A 46 100.680 6.340 90.048 1.00 0.00 xxxx 349 ATOM 350 C SER A 46 101.150 4.901 90.204 1.00 0.00 xxxx 350 ATOM 351 O SER A 46 102.185 4.522 89.662 1.00 0.00 xxxx 351 ATOM 352 CB SER A 46 101.059 7.151 91.287 1.00 0.00 xxxx 352 ATOM 353 OG SER A 46 100.720 8.514 91.110 1.00 0.00 xxxx 353 ATOM 354 N LYS A 47 100.378 4.093 90.931 1.00 0.00 xxxx 354 ATOM 355 CA LYS A 47 100.684 2.667 91.039 1.00 0.00 xxxx 355 ATOM 356 C LYS A 47 100.614 1.975 89.685 1.00 0.00 xxxx 356 ATOM 357 O LYS A 47 101.463 1.146 89.362 1.00 0.00 xxxx 357 ATOM 358 CB LYS A 47 99.735 1.977 92.029 1.00 0.00 xxxx 358 ATOM 359 CG LYS A 47 99.961 2.404 93.475 1.00 0.00 xxxx 359 ATOM 360 CD LYS A 47 98.985 1.704 94.410 1.00 0.00 xxxx 360 ATOM 361 CE LYS A 47 99.264 2.081 95.854 1.00 0.00 xxxx 361 ATOM 362 NZ LYS A 47 98.268 1.501 96.800 1.00 0.00 xxxx 362 ATOM 363 N GLN A 48 99.592 2.305 88.898 1.00 0.00 xxxx 363 ATOM 364 CA GLN A 48 99.460 1.726 87.578 1.00 0.00 xxxx 364 ATOM 365 C GLN A 48 100.663 2.079 86.686 1.00 0.00 xxxx 365 ATOM 366 O GLN A 48 101.166 1.233 85.952 1.00 0.00 xxxx 366 ATOM 367 CB GLN A 48 98.160 2.189 86.915 1.00 0.00 xxxx 367 ATOM 368 CG GLN A 48 97.943 1.513 85.563 1.00 0.00 xxxx 368 ATOM 369 CD GLN A 48 96.543 1.713 85.022 1.00 0.00 xxxx 369 ATOM 370 OE1 GLN A 48 96.302 2.594 84.194 1.00 0.00 xxxx 370 ATOM 371 NE2 GLN A 48 95.611 0.888 85.477 1.00 0.00 xxxx 371 ATOM 372 N ASN A 49 101.128 3.320 86.760 1.00 0.00 xxxx 372 ATOM 373 CA ASN A 49 102.247 3.745 85.917 1.00 0.00 xxxx 373 ATOM 374 C ASN A 49 103.500 2.936 86.271 1.00 0.00 xxxx 374 ATOM 375 O ASN A 49 104.240 2.525 85.382 1.00 0.00 xxxx 375 ATOM 376 CB ASN A 49 102.506 5.251 86.061 1.00 0.00 xxxx 376 ATOM 377 CG ASN A 49 101.367 6.102 85.492 1.00 0.00 xxxx 377 ATOM 378 OD1 ASN A 49 100.536 5.616 84.729 1.00 0.00 xxxx 378 ATOM 379 ND2 ASN A 49 101.333 7.379 85.870 1.00 0.00 xxxx 379 ATOM 380 N ASP A 50 103.725 2.698 87.562 1.00 0.00 xxxx 380 ATOM 381 CA ASP A 50 104.856 1.874 87.982 1.00 0.00 xxxx 381 ATOM 382 C ASP A 50 104.697 0.440 87.487 1.00 0.00 xxxx 382 ATOM 383 O ASP A 50 105.672 −0.216 87.089 1.00 0.00 xxxx 383 ATOM 384 CB ASP A 50 104.998 1.875 89.502 1.00 0.00 xxxx 384 ATOM 385 CG ASP A 50 105.413 3.222 90.053 1.00 0.00 xxxx 385 ATOM 386 OD1 ASP A 50 105.848 4.091 89.267 1.00 0.00 xxxx 386 ATOM 387 OD2 ASP A 50 105.311 3.403 91.286 1.00 0.00 xxxx 387 ATOM 388 N GLN A 51 103.464 −0.055 87.526 1.00 0.00 xxxx 388 ATOM 389 CA GLN A 51 103.189 −1.410 87.060 1.00 0.00 xxxx 389 ATOM 390 C GLN A 51 103.516 −1.541 85.581 1.00 0.00 xxxx 390 ATOM 391 O GLN A 51 104.057 −2.559 85.142 1.00 0.00 xxxx 391 ATOM 392 CB GLN A 51 101.725 −1.778 87.334 1.00 0.00 xxxx 392 ATOM 393 CG GLN A 51 101.498 −2.034 88.824 1.00 0.00 xxxx 393 ATOM 394 CD GLN A 51 100.046 −2.147 89.231 1.00 0.00 xxxx 394 ATOM 395 OE1 GLN A 51 99.148 −1.628 88.557 1.00 0.00 xxxx 395 ATOM 396 NE2 GLN A 51 99.806 −2.809 90.361 1.00 0.00 xxxx 396 ATOM 397 N ILE A 52 103.182 −0.515 84.811 1.00 0.00 xxxx 397 ATOM 398 CA ILE A 52 103.475 −0.559 83.388 1.00 0.00 xxxx 398 ATOM 399 C ILE A 52 104.991 −0.557 83.135 1.00 0.00 xxxx 399 ATOM 400 O ILE A 52 105.474 −1.287 82.267 1.00 0.00 xxxx 400 ATOM 401 CB ILE A 52 102.741 0.587 82.668 1.00 0.00 xxxx 401 ATOM 402 CG1 ILE A 52 101.226 0.330 82.728 1.00 0.00 xxxx 402 ATOM 403 CG2 ILE A 52 103.220 0.723 81.220 1.00 0.00 xxxx 403 ATOM 404 CD1 ILE A 52 100.376 1.551 82.399 1.00 0.00 xxxx 404 ATOM 405 N ASP A 53 105.747 0.215 83.917 1.00 0.00 xxxx 405 ATOM 406 CA ASP A 53 107.214 0.162 83.824 1.00 0.00 xxxx 406 ATOM 407 C ASP A 53 107.728 −1.266 84.031 1.00 0.00 xxxx 407 ATOM 408 O ASP A 53 108.629 −1.727 83.310 1.00 0.00 xxxx 408 ATOM 409 CB ASP A 53 107.869 1.079 84.857 1.00 0.00 xxxx 409 ATOM 410 CG ASP A 53 107.717 2.547 84.531 1.00 0.00 xxxx 410 ATOM 411 OD1 ASP A 53 107.558 2.886 83.345 1.00 0.00 xxxx 411 ATOM 412 OD2 ASP A 53 107.786 3.365 85.474 1.00 0.00 xxxx 412 ATOM 413 N VAL A 54 107.188 −1.952 85.036 1.00 0.00 xxxx 413 ATOM 414 CA VAL A 54 107.601 −3.323 85.328 1.00 0.00 xxxx 414 ATOM 415 C VAL A 54 107.221 −4.290 84.200 1.00 0.00 xxxx 415 ATOM 416 O VAL A 54 108.024 −5.137 83.808 1.00 0.00 xxxx 416 ATOM 417 CB VAL A 54 107.011 −3.791 86.677 1.00 0.00 xxxx 417 ATOM 418 CG1 VAL A 54 107.249 −5.283 86.887 1.00 0.00 xxxx 418 ATOM 419 CG2 VAL A 54 107.617 −2.982 87.823 1.00 0.00 xxxx 419 ATOM 420 N LEU A 55 106.011 −4.156 83.664 1.00 0.00 xxxx 420 ATOM 421 CA LEU A 55 105.582 −5.031 82.577 1.00 0.00 xxxx 421 ATOM 422 C LEU A 55 106.493 −4.847 81.362 1.00 0.00 xxxx 422 ATOM 423 O LEU A 55 106.877 −5.820 80.704 1.00 0.00 xxxx 423 ATOM 424 CB LEU A 55 104.120 −4.747 82.216 1.00 0.00 xxxx 424 ATOM 425 CG LEU A 55 103.107 −5.160 83.289 1.00 0.00 xxxx 425 ATOM 426 CD1 LEU A 55 101.717 −4.586 83.008 1.00 0.00 xxxx 426 ATOM 427 CD2 LEU A 55 103.031 −6.669 83.414 1.00 0.00 xxxx 427 ATOM 428 N LEU A 56 106.841 −3.599 81.059 1.00 0.00 xxxx 428 ATOM 429 CA LEU A 56 107.753 −3.336 79.949 1.00 0.00 xxxx 429 ATOM 430 C LEU A 56 109.150 −3.903 80.226 1.00 0.00 xxxx 430 ATOM 431 O LEU A 56 109.793 −4.445 79.325 1.00 0.00 xxxx 431 ATOM 432 CB LEU A 56 107.814 −1.839 79.657 1.00 0.00 xxxx 432 ATOM 433 CG LEU A 56 106.512 −1.310 79.039 1.00 0.00 xxxx 433 ATOM 434 CD1 LEU A 56 106.505 0.221 78.986 1.00 0.00 xxxx 434 ATOM 435 CD2 LEU A 56 106.269 −1.906 77.650 1.00 0.00 xxxx 435 ATOM 436 N ALA A 57 109.615 −3.812 81.472 1.00 0.00 xxxx 436 ATOM 437 CA ALA A 57 110.899 −4.396 81.829 1.00 0.00 xxxx 437 ATOM 438 C ALA A 57 110.876 −5.912 81.636 1.00 0.00 xxxx 438 ATOM 439 O ALA A 57 111.914 −6.521 81.319 1.00 0.00 xxxx 439 ATOM 440 CB ALA A 57 111.272 −4.039 83.279 1.00 0.00 xxxx 440 ATOM 441 N LYS A 58 109.699 −6.511 81.821 1.00 0.00 xxxx 441 ATOM 442 CA LYS A 58 109.515 −7.953 81.661 1.00 0.00 xxxx 442 ATOM 443 C LYS A 58 109.301 −8.363 80.208 1.00 0.00 xxxx 443 ATOM 444 O LYS A 58 109.065 −9.536 79.919 1.00 0.00 xxxx 444 ATOM 445 CB LYS A 58 108.349 −8.439 82.523 1.00 0.00 xxxx 445 ATOM 446 CG LYS A 58 108.644 −8.364 84.017 1.00 0.00 xxxx 446 ATOM 447 CD LYS A 58 107.485 −8.852 84.854 1.00 0.00 xxxx 447 ATOM 448 CE LYS A 58 107.877 −8.918 86.324 1.00 0.00 xxxx 448 ATOM 449 NZ LYS A 58 106.777 −9.443 87.171 1.00 0.00 xxxx 449 ATOM 450 N GLY A 59 109.405 −7.399 79.300 1.00 0.00 xxxx 450 ATOM 451 CA GLY A 59 109.364 −7.687 77.882 1.00 0.00 xxxx 451 ATOM 452 C GLY A 59 108.011 −8.128 77.353 1.00 0.00 xxxx 452 ATOM 453 O GLY A 59 107.951 −8.956 76.442 1.00 0.00 xxxx 453 ATOM 454 N VAL A 60 106.925 −7.596 77.908 1.00 0.00 xxxx 454 ATOM 455 CA VAL A 60 105.607 −7.915 77.365 1.00 0.00 xxxx 455 ATOM 456 C VAL A 60 105.555 −7.444 75.916 1.00 0.00 xxxx 456 ATOM 457 O VAL A 60 106.153 −6.430 75.552 1.00 0.00 xxxx 457 ATOM 458 CB VAL A 60 104.460 −7.298 78.184 1.00 0.00 xxxx 458 ATOM 459 CG1 VAL A 60 104.425 −7.880 79.587 1.00 0.00 xxxx 459 ATOM 460 CG2 VAL A 60 104.512 −5.757 78.190 1.00 0.00 xxxx 460 ATOM 461 N LYS A 61 104.831 −8.195 75.093 1.00 0.00 xxxx 461 ATOM 462 CA LYS A 61 104.708 −7.860 73.679 1.00 0.00 xxxx 462 ATOM 463 C LYS A 61 103.444 −7.049 73.388 1.00 0.00 xxxx 463 ATOM 464 O LYS A 61 103.270 −6.551 72.280 1.00 0.00 xxxx 464 ATOM 465 CB LYS A 61 104.736 −9.135 72.830 1.00 0.00 xxxx 465 ATOM 466 CG LYS A 61 106.049 −9.896 72.930 1.00 0.00 xxxx 466 ATOM 467 CD LYS A 61 106.112 −11.014 71.902 1.00 0.00 xxxx 467 ATOM 468 CE LYS A 61 106.273 −10.456 70.491 1.00 0.00 xxxx 468 ATOM 469 NZ LYS A 61 106.157 −11.505 69.426 1.00 0.00 xxxx 469 ATOM 470 N ALA A 62 102.561 −6.938 74.374 1.00 0.00 xxxx 470 ATOM 471 CA ALA A 62 101.392 −6.064 74.278 1.00 0.00 xxxx 471 ATOM 472 C ALA A 62 100.930 −5.706 75.670 1.00 0.00 xxxx 472 ATOM 473 O ALA A 62 101.185 −6.447 76.623 1.00 0.00 xxxx 473 ATOM 474 CB ALA A 62 100.254 −6.732 73.503 1.00 0.00 xxxx 474 ATOM 475 N LEU A 63 100.280 −4.553 75.787 1.00 0.00 xxxx 475 ATOM 476 CA LEU A 63 99.649 −4.122 77.034 1.00 0.00 xxxx 476 ATOM 477 C LEU A 63 98.146 −3.994 76.833 1.00 0.00 xxxx 477 ATOM 478 O LEU A 63 97.712 −3.472 75.820 1.00 0.00 xxxx 478 ATOM 479 CB LEU A 63 100.211 −2.774 77.479 1.00 0.00 xxxx 479 ATOM 480 CG LEU A 63 101.669 −2.776 77.919 1.00 0.00 xxxx 480 ATOM 481 CD1 LEU A 63 102.226 −1.365 77.884 1.00 0.00 xxxx 481 ATOM 482 CD2 LEU A 63 101.797 −3.368 79.321 1.00 0.00 xxxx 482 ATOM 483 N ALA A 64 97.360 −4.466 77.798 1.00 0.00 xxxx 483 ATOM 484 CA ALA A 64 95.934 −4.163 77.857 1.00 0.00 xxxx 484 ATOM 485 C ALA A 64 95.720 −3.374 79.139 1.00 0.00 xxxx 485 ATOM 486 O ALA A 64 95.967 −3.887 80.233 1.00 0.00 xxxx 486 ATOM 487 CB ALA A 64 95.091 −5.442 77.841 1.00 0.00 xxxx 487 ATOM 488 N ILE A 65 95.281 −2.125 79.008 1.00 0.00 xxxx 488 ATOM 489 CA ILE A 65 95.305 −1.184 80.125 1.00 0.00 xxxx 489 ATOM 490 C ILE A 65 93.900 −0.669 80.430 1.00 0.00 xxxx 490 ATOM 491 O ILE A 65 93.240 −0.078 79.579 1.00 0.00 xxxx 491 ATOM 492 CB ILE A 65 96.250 0.003 79.819 1.00 0.00 xxxx 492 ATOM 493 CG1 ILE A 65 97.671 −0.497 79.500 1.00 0.00 xxxx 493 ATOM 494 CG2 ILE A 65 96.178 1.044 80.964 1.00 0.00 xxxx 494 ATOM 495 CD1 ILE A 65 98.341 −1.250 80.648 1.00 0.00 xxxx 495 ATOM 496 N ASN A 66 93.433 −0.941 81.640 1.00 0.00 xxxx 496 ATOM 497 CA ASN A 66 92.196 −0.377 82.162 1.00 0.00 xxxx 497 ATOM 498 C ASN A 66 92.595 0.789 83.070 1.00 0.00 xxxx 498 ATOM 499 O ASN A 66 92.954 0.574 84.227 1.00 0.00 xxxx 499 ATOM 500 CB ASN A 66 91.427 −1.500 82.892 1.00 0.00 xxxx 500 ATOM 501 CG ASN A 66 90.188 −1.022 83.635 1.00 0.00 xxxx 501 ATOM 502 OD1 ASN A 66 89.988 −1.389 84.797 1.00 0.00 xxxx 502 ATOM 503 ND2 ASN A 66 89.317 −0.271 82.953 1.00 0.00 xxxx 503 ATOM 504 N LEU A 67 92.595 2.007 82.519 1.00 0.00 xxxx 504 ATOM 505 CA LEU A 67 93.111 3.187 83.213 1.00 0.00 xxxx 505 ATOM 506 C LEU A 67 92.402 3.474 84.526 1.00 0.00 xxxx 506 ATOM 507 O LEU A 67 91.196 3.295 84.638 1.00 0.00 xxxx 507 ATOM 508 CB LEU A 67 92.999 4.416 82.306 1.00 0.00 xxxx 508 ATOM 509 CG LEU A 67 93.959 4.418 81.114 1.00 0.00 xxxx 509 ATOM 510 CD1 LEU A 67 93.473 5.426 80.071 1.00 0.00 xxxx 510 ATOM 511 CD2 LEU A 67 95.356 4.773 81.575 1.00 0.00 xxxx 511 ATOM 512 N VAL A 68 93.164 3.908 85.529 1.00 0.00 xxxx 512 ATOM 513 CA VAL A 68 92.548 4.499 86.712 1.00 0.00 xxxx 513 ATOM 514 C VAL A 68 92.007 5.883 86.328 1.00 0.00 xxxx 514 ATOM 515 O VAL A 68 90.839 6.205 86.572 1.00 0.00 xxxx 515 ATOM 516 CB VAL A 68 93.543 4.601 87.879 1.00 0.00 xxxx 516 ATOM 517 CG1 VAL A 68 92.888 5.299 89.074 1.00 0.00 xxxx 517 ATOM 518 CG2 VAL A 68 94.045 3.214 88.276 1.00 0.00 xxxx 518 ATOM 519 N ASP A 69 92.881 6.688 85.728 1.00 0.00 xxxx 519 ATOM 520 CA ASP A 69 92.566 8.048 85.273 1.00 0.00 xxxx 520 ATOM 521 C ASP A 69 92.653 8.091 83.749 1.00 0.00 xxxx 521 ATOM 522 O ASP A 69 93.722 7.908 83.182 1.00 0.00 xxxx 522 ATOM 523 CB ASP A 69 93.534 9.049 85.904 1.00 0.00 xxxx 523 ATOM 524 CG ASP A 69 93.300 10.481 85.454 1.00 0.00 xxxx 524 ATOM 525 OD1 ASP A 69 92.338 10.757 84.700 1.00 0.00 xxxx 525 ATOM 526 OD2 ASP A 69 94.096 11.344 85.886 1.00 0.00 xxxx 526 ATOM 527 N PRO A 70 91.519 8.324 83.081 1.00 0.00 xxxx 527 ATOM 528 CA PRO A 70 91.546 8.357 81.613 1.00 0.00 xxxx 528 ATOM 529 C PRO A 70 92.534 9.376 81.041 1.00 0.00 xxxx 529 ATOM 530 O PRO A 70 93.051 9.184 79.938 1.00 0.00 xxxx 530 ATOM 531 CB PRO A 70 90.108 8.731 81.247 1.00 0.00 xxxx 531 ATOM 532 CG PRO A 70 89.289 8.251 82.394 1.00 0.00 xxxx 532 ATOM 533 CD PRO A 70 90.154 8.424 83.624 1.00 0.00 xxxx 533 ATOM 534 N ALA A 71 92.813 10.440 81.784 1.00 0.00 xxxx 534 ATOM 535 CA ALA A 71 93.717 11.475 81.292 1.00 0.00 xxxx 535 ATOM 536 C ALA A 71 95.163 10.987 81.229 1.00 0.00 xxxx 536 ATOM 537 O ALA A 71 96.015 11.647 80.638 1.00 0.00 xxxx 537 ATOM 538 CB ALA A 71 93.618 12.724 82.166 1.00 0.00 xxxx 538 ATOM 539 N ALA A 72 95.439 9.831 81.834 1.00 0.00 xxxx 539 ATOM 540 CA ALA A 72 96.795 9.299 81.874 1.00 0.00 xxxx 540 ATOM 541 C ALA A 72 97.136 8.467 80.655 1.00 0.00 xxxx 541 ATOM 542 O ALA A 72 98.216 7.874 80.598 1.00 0.00 xxxx 542 ATOM 543 CB ALA A 72 96.998 8.462 83.127 1.00 0.00 xxxx 543 ATOM 544 N ALA A 73 96.221 8.396 79.693 1.00 0.00 xxxx 544 ATOM 545 CA ALA A 73 96.492 7.631 78.472 1.00 0.00 xxxx 545 ATOM 546 C ALA A 73 97.802 8.065 77.811 1.00 0.00 xxxx 546 ATOM 547 O ALA A 73 98.565 7.229 77.328 1.00 0.00 xxxx 547 ATOM 548 CB ALA A 73 95.333 7.765 77.492 1.00 0.00 xxxx 548 ATOM 549 N GLY A 74 98.058 9.373 77.788 1.00 0.00 xxxx 549 ATOM 550 CA GLY A 74 99.286 9.886 77.203 1.00 0.00 xxxx 550 ATOM 551 C GLY A 74 100.541 9.357 77.875 1.00 0.00 xxxx 551 ATOM 552 O GLY A 74 101.514 8.988 77.214 1.00 0.00 xxxx 552 ATOM 553 N THR A 75 100.518 9.335 79.204 1.00 0.00 xxxx 553 ATOM 554 CA THR A 75 101.631 8.825 79.990 1.00 0.00 xxxx 554 ATOM 555 C THR A 75 101.904 7.368 79.631 1.00 0.00 xxxx 555 ATOM 556 O THR A 75 103.051 6.971 79.433 1.00 0.00 xxxx 556 ATOM 557 CB THR A 75 101.340 8.945 81.489 1.00 0.00 xxxx 557 ATOM 558 OG1 THR A 75 101.223 10.330 81.831 1.00 0.00 xxxx 558 ATOM 559 CG2 THR A 75 102.458 8.299 82.317 1.00 0.00 xxxx 559 ATOM 560 N VAL A 76 100.838 6.576 79.550 1.00 0.00 xxxx 560 ATOM 561 CA VAL A 76 100.961 5.165 79.228 1.00 0.00 xxxx 561 ATOM 562 C VAL A 76 101.516 4.973 77.818 1.00 0.00 xxxx 562 ATOM 563 O VAL A 76 102.418 4.160 77.598 1.00 0.00 xxxx 563 ATOM 564 CB VAL A 76 99.600 4.457 79.384 1.00 0.00 xxxx 564 ATOM 565 CG1 VAL A 76 99.679 3.013 78.879 1.00 0.00 xxxx 565 ATOM 566 CG2 VAL A 76 99.164 4.498 80.850 1.00 0.00 xxxx 566 ATOM 567 N ILE A 77 100.990 5.747 76.874 1.00 0.00 xxxx 567 ATOM 568 CA ILE A 77 101.426 5.663 75.477 1.00 0.00 xxxx 568 ATOM 569 C ILE A 77 102.916 5.991 75.341 1.00 0.00 xxxx 569 ATOM 570 O ILE A 77 103.650 5.327 74.601 1.00 0.00 xxxx 570 ATOM 571 CB ILE A 77 100.580 6.595 74.594 1.00 0.00 xxxx 571 ATOM 572 CG1 ILE A 77 99.207 5.972 74.345 1.00 0.00 xxxx 572 ATOM 573 CG2 ILE A 77 101.303 6.905 73.287 1.00 0.00 xxxx 573 ATOM 574 CD1 ILE A 77 98.218 6.927 73.704 1.00 0.00 xxxx 574 ATOM 575 N GLU A 78 103.371 7.007 76.065 1.00 0.00 xxxx 575 ATOM 576 C GLU A 78 105.680 6.225 76.455 1.00 0.00 xxxx 576 ATOM 577 0 GLU A 78 106.718 5.967 75.839 1.00 0.00 xxxx 577 ATOM 578 CA GLU A 78 104.781 7.389 76.018 1.00 0.00 xxxx 578 ATOM 579 CB GLU A 78 105.029 8.620 76.899 1.00 0.00 xxxx 579 ATOM 580 CG GLU A 78 106.383 9.281 76.690 1.00 0.00 xxxx 580 ATOM 581 CD GLU A 78 107.463 8.732 77.605 1.00 0.00 xxxx 581 ATOM 582 OE1 GLU A 78 107.122 8.181 78.674 1.00 0.00 xxxx 582 ATOM 583 OE2 GLU A 78 108.658 8.853 77.255 1.00 0.00 xxxx 583 ATOM 584 N LYS A 79 105.275 5.512 77.504 1.00 0.00 xxxx 584 ATOM 585 CA LYS A 79 106.071 4.387 77.979 1.00 0.00 xxxx 585 ATOM 586 C LYS A 79 106.086 3.283 76.931 1.00 0.00 xxxx 586 ATOM 587 O LYS A 79 107.145 2.742 76.596 1.00 0.00 xxxx 587 ATOM 588 CB LYS A 79 105.533 3.860 79.310 1.00 0.00 xxxx 588 ATOM 589 CG LYS A 79 105.667 4.829 80.472 1.00 0.00 xxxx 589 ATOM 590 CD LYS A 79 104.967 4.284 81.707 1.00 0.00 xxxx 590 ATOM 591 CE LYS A 79 105.041 5.261 82.886 1.00 0.00 xxxx 591 ATOM 592 NZ LYS A 79 106.441 5.513 83.323 1.00 0.00 xxxx 592 ATOM 593 N ALA A 80 104.912 2.963 76.396 1.00 0.00 xxxx 593 ATOM 594 CA ALA A 80 104.798 1.881 75.427 1.00 0.00 xxxx 594 ATOM 595 C ALA A 80 105.539 2.204 74.126 1.00 0.00 xxxx 595 ATOM 596 O ALA A 80 106.202 1.333 73.546 1.00 0.00 xxxx 596 ATOM 597 CB ALA A 80 103.346 1.591 75.143 1.00 0.00 xxxx 597 ATOM 598 O ARG A 81 108.081 3.246 71.373 1.00 0.00 xxxx 598 ATOM 599 N ARG A 81 105.423 3.453 73.679 1.00 0.00 xxxx 599 ATOM 600 CA ARG A 81 106.016 3.886 72.408 1.00 0.00 xxxx 600 ATOM 601 C ARG A 81 107.524 3.653 72.391 1.00 0.00 xxxx 601 ATOM 602 CB ARG A 81 105.708 5.365 72.151 1.00 0.00 xxxx 602 ATOM 603 CG ARG A 81 106.197 5.872 70.789 1.00 0.00 xxxx 603 ATOM 604 CD ARG A 81 106.272 7.394 70.728 1.00 0.00 xxxx 604 ATOM 605 NE ARG A 81 105.027 8.050 71.122 1.00 0.00 xxxx 605 ATOM 606 CZ ARG A 81 104.003 8.258 70.302 1.00 0.00 xxxx 606 ATOM 607 NH1 ARG A 81 102.913 8.870 70.752 1.00 0.00 xxxx 607 ATOM 608 NH2 ARG A 81 104.058 7.843 69.041 1.00 0.00 xxxx 608 ATOM 609 N GLY A 82 108.172 3.884 73.530 1.00 0.00 xxxx 609 ATOM 610 CA GLY A 82 109.614 3.736 73.627 1.00 0.00 xxxx 610 ATOM 611 C GLY A 82 110.090 2.319 73.370 1.00 0.00 xxxx 611 ATOM 612 O GLY A 82 111.231 2.085 72.969 1.00 0.00 xxxx 612 ATOM 613 N GLN A 83 109.204 1.360 73.605 1.00 0.00 xxxx 613 ATOM 614 CA GLN A 83 109.538 −0.043 73.423 1.00 0.00 xxxx 614 ATOM 615 C GLN A 83 108.786 −0.651 72.231 1.00 0.00 xxxx 615 ATOM 616 O GLN A 83 108.819 −1.862 72.010 1.00 0.00 xxxx 616 ATOM 617 CB GLN A 83 109.222 −0.811 74.710 1.00 0.00 xxxx 617 ATOM 618 CG GLN A 83 110.081 −2.042 74.937 1.00 0.00 xxxx 618 ATOM 619 CD GLN A 83 110.165 −2.422 76.404 1.00 0.00 xxxx 619 ATOM 620 OE1 GLN A 83 110.622 −1.635 77.235 1.00 0.00 xxxx 620 ATOM 621 NE2 GLN A 83 109.712 −3.626 76.730 1.00 0.00 xxxx 621 ATOM 622 N ASN A 84 108.101 0.202 71.474 1.00 0.00 xxxx 622 ATOM 623 CA ASN A 84 107.310 −0.224 70.321 1.00 0.00 xxxx 623 ATOM 624 C ASN A 84 106.233 −1.246 70.709 1.00 0.00 xxxx 624 ATOM 625 O ASN A 84 105.928 −2.157 69.939 1.00 0.00 xxxx 625 ATOM 626 CB ASN A 84 108.221 −0.799 69.228 1.00 0.00 xxxx 626 ATOM 627 CG ASN A 84 109.380 0.118 68.896 1.00 0.00 xxxx 627 ATOM 628 OD1 ASN A 84 109.186 1.296 68.588 1.00 0.00 xxxx 628 ATOM 629 ND2 ASN A 84 110.600 −0.413 68.978 1.00 0.00 xxxx 629 ATOM 630 N VAL A 85 105.647 −1.074 71.891 1.00 0.00 xxxx 630 ATOM 631 CA VAL A 85 104.676 −2.033 72.419 1.00 0.00 xxxx 631 ATOM 632 C VAL A 85 103.254 −1.525 72.172 1.00 0.00 xxxx 632 ATOM 633 O VAL A 85 102.932 −0.393 72.508 1.00 0.00 xxxx 633 ATOM 634 CB VAL A 85 104.952 −2.294 73.920 1.00 0.00 xxxx 634 ATOM 635 CG1 VAL A 85 103.787 −3.044 74.592 1.00 0.00 xxxx 635 ATOM 636 CG2 VAL A 85 106.258 −3.072 74.068 1.00 0.00 xxxx 636 ATOM 637 N PRO A 86 102.388 −2.363 71.577 1.00 0.00 xxxx 637 ATOM 638 CA PRO A 86 101.004 −1.920 71.366 1.00 0.00 xxxx 638 ATOM 639 C PRO A 86 100.209 −1.854 72.666 1.00 0.00 xxxx 639 ATOM 640 O PRO A 86 100.501 −2.592 73.621 1.00 0.00 xxxx 640 ATOM 641 CB PRO A 86 100.421 −2.989 70.437 1.00 0.00 xxxx 641 ATOM 642 CG PRO A 86 101.291 −4.205 70.660 1.00 0.00 xxxx 642 ATOM 643 CD PRO A 86 102.672 −3.668 70.951 1.00 0.00 xxxx 643 ATOM 644 N VAL A 87 99.215 −0.973 72.707 1.00 0.00 xxxx 644 ATOM 645 CA VAL A 87 98.377 −0.792 73.891 1.00 0.00 xxxx 645 ATOM 646 C VAL A 87 96.907 −0.896 73.513 1.00 0.00 xxxx 646 ATOM 647 O VAL A 87 96.432 −0.123 72.687 1.00 0.00 xxxx 647 ATOM 648 CB VAL A 87 98.626 0.567 74.572 1.00 0.00 xxxx 648 ATOM 649 CG1 VAL A 87 97.751 0.707 75.828 1.00 0.00 xxxx 649 ATOM 650 CG2 VAL A 87 100.070 0.724 74.941 1.00 0.00 xxxx 650 ATOM 651 N VAL A 88 96.192 −1.820 74.149 1.00 0.00 xxxx 651 ATOM 652 CA VAL A 88 94.740 −1.888 74.015 1.00 0.00 xxxx 652 ATOM 653 C VAL A 88 94.141 −1.351 75.308 1.00 0.00 xxxx 653 ATOM 654 O VAL A 88 94.129 −2.049 76.335 1.00 0.00 xxxx 654 ATOM 655 CB VAL A 88 94.255 −3.317 73.725 1.00 0.00 xxxx 655 ATOM 656 CG1 VAL A 88 92.734 −3.331 73.544 1.00 0.00 xxxx 656 ATOM 657 CG2 VAL A 88 94.938 −3.884 72.472 1.00 0.00 xxxx 657 ATOM 658 N PHE A 89 93.667 −0.108 75.279 1.00 0.00 xxxx 658 ATOM 659 CA PHE A 89 92.946 0.445 76.426 1.00 0.00 xxxx 659 ATOM 660 C PHE A 89 91.574 −0.204 76.508 1.00 0.00 xxxx 660 ATOM 661 O PHE A 89 90.982 −0.520 75.470 1.00 0.00 xxxx 661 ATOM 662 CB PHE A 89 92.804 1.958 76.293 1.00 0.00 xxxx 662 ATOM 663 CG PHE A 89 94.107 2.702 76.394 1.00 0.00 xxxx 663 ATOM 664 CD1 PHE A 89 94.708 2.899 77.625 1.00 0.00 xxxx 664 ATOM 665 CD2 PHE A 89 94.734 3.190 75.259 1.00 0.00 xxxx 665 ATOM 666 CE1 PHE A 89 95.910 3.578 77.726 1.00 0.00 xxxx 666 ATOM 667 CE2 PHE A 89 95.936 3.879 75.355 1.00 0.00 xxxx 667 ATOM 668 CZ PHE A 89 96.523 4.077 76.594 1.00 0.00 xxxx 668 ATOM 669 N PHE A 90 91.048 −0.413 77.712 1.00 0.00 xxxx 669 ATOM 670 CA PHE A 90 89.680 −0.944 77.785 1.00 0.00 xxxx 670 ATOM 671 C PHE A 90 88.926 −0.412 78.992 1.00 0.00 xxxx 671 ATOM 672 O PHE A 90 89.525 −0.062 80.010 1.00 0.00 xxxx 672 ATOM 673 CB PHE A 90 89.660 −2.510 77.730 1.00 0.00 xxxx 673 ATOM 674 CG PHE A 90 90.339 −3.225 78.894 1.00 0.00 xxxx 674 ATOM 675 CD1 PHE A 90 89.573 −3.927 79.824 1.00 0.00 xxxx 675 ATOM 676 CD2 PHE A 90 91.729 −3.261 79.015 1.00 0.00 xxxx 676 ATOM 677 CE1 PHE A 90 90.184 −4.611 80.886 1.00 0.00 xxxx 677 ATOM 678 CE2 PHE A 90 92.349 −3.934 80.071 1.00 0.00 xxxx 678 ATOM 679 CZ PHE A 90 91.574 −4.614 81.001 1.00 0.00 xxxx 679 ATOM 680 N ASN A 91 87.616 −0.279 78.791 1.00 0.00 xxxx 680 ATOM 681 CA ASN A 91 86.590 0.085 79.786 1.00 0.00 xxxx 681 ATOM 682 C ASN A 91 86.587 1.542 80.258 1.00 0.00 xxxx 682 ATOM 683 O ASN A 91 85.510 2.087 80.492 1.00 0.00 xxxx 683 ATOM 684 CB ASN A 91 86.660 −0.854 80.998 1.00 0.00 xxxx 684 ATOM 685 CG ASN A 91 85.830 −0.351 82.182 1.00 0.00 xxxx 685 ATOM 686 OD1 ASN A 91 86.370 0.228 83.120 1.00 0.00 xxxx 686 ATOM 687 ND2 ASN A 91 84.522 −0.592 82.147 1.00 0.00 xxxx 687 ATOM 688 N LYS A 92 87.752 2.160 80.423 1.00 0.00 xxxx 688 ATOM 689 CA LYS A 92 87.828 3.594 80.690 1.00 0.00 xxxx 689 ATOM 690 C LYS A 92 88.391 4.250 79.446 1.00 0.00 xxxx 690 ATOM 691 O LYS A 92 89.554 4.061 79.097 1.00 0.00 xxxx 691 ATOM 692 CB LYS A 92 88.682 3.903 81.918 1.00 0.00 xxxx 692 ATOM 693 CG LYS A 92 88.035 3.444 83.217 1.00 0.00 xxxx 693 ATOM 694 CD LYS A 92 88.252 4.447 84.327 1.00 0.00 xxxx 694 ATOM 695 CE LYS A 92 88.017 3.795 85.679 1.00 0.00 xxxx 695 ATOM 696 NZ LYS A 92 88.338 4.731 86.803 1.00 0.00 xxxx 696 ATOM 697 N GLU A 93 87.546 5.014 78.770 1.00 0.00 xxxx 697 ATOM 698 CA GLU A 93 87.872 5.464 77.422 1.00 0.00 xxxx 698 ATOM 699 C GLU A 93 88.806 6.685 77.393 1.00 0.00 xxxx 699 ATOM 700 O GLU A 93 88.495 7.729 77.986 1.00 0.00 xxxx 700 ATOM 701 CB GLU A 93 86.585 5.765 76.656 1.00 0.00 xxxx 701 ATOM 702 CG GLU A 93 86.840 6.151 75.212 1.00 0.00 xxxx 702 ATOM 703 CD GLU A 93 85.572 6.254 74.396 1.00 0.00 xxxx 703 ATOM 704 OE1 GLU A 93 84.503 5.840 74.887 1.00 0.00 xxxx 704 ATOM 705 OE2 GLU A 93 85.652 6.749 73.252 1.00 0.00 xxxx 705 ATOM 706 N PRO A 94 89.950 6.563 76.701 1.00 0.00 xxxx 706 ATOM 707 CA PRO A 94 90.860 7.705 76.521 1.00 0.00 xxxx 707 ATOM 708 C PRO A 94 90.311 8.706 75.520 1.00 0.00 xxxx 708 ATOM 709 O PRO A 94 89.374 8.385 74.787 1.00 0.00 xxxx 709 ATOM 710 CB PRO A 94 92.143 7.073 75.966 1.00 0.00 xxxx 710 ATOM 711 CG PRO A 94 91.946 5.593 76.036 1.00 0.00 xxxx 711 ATOM 712 CD PRO A 94 90.473 5.342 76.071 1.00 0.00 xxxx 712 ATOM 713 N SER A 95 90.901 9.897 75.465 1.00 0.00 xxxx 713 ATOM 714 CA SER A 95 90.489 10.879 74.474 1.00 0.00 xxxx 714 ATOM 715 C SER A 95 90.814 10.412 73.058 1.00 0.00 xxxx 715 ATOM 716 O SER A 95 91.716 9.616 72.837 1.00 0.00 xxxx 716 ATOM 717 CB SER A 95 91.157 12.234 74.741 1.00 0.00 xxxx 717 ATOM 718 OG SER A 95 92.546 12.172 74.450 1.00 0.00 xxxx 718 ATOM 719 N ARG A 96 90.052 10.923 72.100 1.00 0.00 xxxx 719 ATOM 720 CA ARG A 96 90.334 10.701 70.685 1.00 0.00 xxxx 720 ATOM 721 C ARG A 96 91.758 11.141 70.337 1.00 0.00 xxxx 721 ATOM 722 O ARG A 96 92.484 10.443 69.625 1.00 0.00 xxxx 722 ATOM 723 CB ARG A 96 89.310 11.451 69.839 1.00 0.00 xxxx 723 ATOM 724 CG ARG A 96 89.369 11.185 68.347 1.00 0.00 xxxx 724 ATOM 725 CD ARG A 96 88.887 9.781 68.062 1.00 0.00 xxxx 725 ATOM 726 NE ARG A 96 89.980 8.914 67.664 1.00 0.00 xxxx 726 ATOM 727 CZ ARG A 96 89.860 7.604 67.479 1.00 0.00 xxxx 727 ATOM 728 NH1 ARG A 96 88.689 7.005 67.678 1.00 0.00 xxxx 728 ATOM 729 NH2 ARG A 96 90.914 6.900 67.099 1.00 0.00 xxxx 729 ATOM 730 N LYS A 97 92.165 12.301 70.845 1.00 0.00 xxxx 730 ATOM 731 CA LYS A 97 93.506 12.809 70.578 1.00 0.00 xxxx 731 ATOM 732 C LYS A 97 94.572 11.850 71.084 1.00 0.00 xxxx 732 ATOM 733 O LYS A 97 95.597 11.648 70.428 1.00 0.00 xxxx 733 ATOM 734 CB LYS A 97 93.707 14.180 71.227 1.00 0.00 xxxx 734 ATOM 735 CG LYS A 97 92.951 15.304 70.545 1.00 0.00 xxxx 735 ATOM 736 CD LYS A 97 93.178 16.635 71.271 1.00 0.00 xxxx 736 ATOM 737 CE LYS A 97 92.407 17.759 70.595 1.00 0.00 xxxx 737 ATOM 738 NZ LYS A 97 92.712 19.098 71.206 1.00 0.00 xxxx 738 ATOM 739 N ALA A 98 94.344 11.277 72.264 1.00 0.00 xxxx 739 ATOM 740 CA ALA A 98 95.304 10.315 72.803 1.00 0.00 xxxx 740 ATOM 741 C ALA A 98 95.394 9.077 71.917 1.00 0.00 xxxx 741 ATOM 742 O ALA A 98 96.488 8.650 71.553 1.00 0.00 xxxx 742 ATOM 743 CB ALA A 98 94.942 9.925 74.237 1.00 0.00 xxxx 743 ATOM 744 N LEU A 99 94.246 8.518 71.551 1.00 0.00 xxxx 744 ATOM 745 CA LEU A 99 94.233 7.346 70.673 1.00 0.00 xxxx 745 ATOM 746 C LEU A 99 94.941 7.608 69.346 1.00 0.00 xxxx 746 ATOM 747 O LEU A 99 95.665 6.754 68.837 1.00 0.00 xxxx 747 ATOM 748 CB LEU A 99 92.801 6.895 70.397 1.00 0.00 xxxx 748 ATOM 749 CG LEU A 99 92.063 6.297 71.584 1.00 0.00 xxxx 749 ATOM 750 CD1 LEU A 99 90.656 5.872 71.158 1.00 0.00 xxxx 750 ATOM 751 CD2 LEU A 99 92.829 5.105 72.167 1.00 0.00 xxxx 751 ATOM 752 N ASP A 100 94.725 8.790 68.779 1.00 0.00 xxxx 752 ATOM 753 CA ASP A 100 95.310 9.129 67.489 1.00 0.00 xxxx 753 ATOM 754 C ASP A 100 96.808 9.421 67.547 1.00 0.00 xxxx 754 ATOM 755 O ASP A 100 97.473 9.473 66.508 1.00 0.00 xxxx 755 ATOM 756 CB ASP A 100 94.579 10.332 66.887 1.00 0.00 xxxx 756 ATOM 757 CG ASP A 100 93.189 9.971 66.389 1.00 0.00 xxxx 757 ATOM 758 OD1 ASP A 100 92.927 8.762 66.198 1.00 0.00 xxxx 758 ATOM 759 OD2 ASP A 100 92.362 10.887 66.199 1.00 0.00 xxxx 759 ATOM 760 N SER A 101 97.343 9.599 68.750 1.00 0.00 xxxx 760 ATOM 761 CA SER A 101 98.739 9.990 68.902 1.00 0.00 xxxx 761 ATOM 762 C SER A 101 99.714 8.818 68.752 1.00 0.00 xxxx 762 ATOM 763 O SER A 101 100.925 9.023 68.654 1.00 0.00 xxxx 763 ATOM 764 CB SER A 101 98.958 10.666 70.263 1.00 0.00 xxxx 764 ATOM 765 OG SER A 101 98.904 9.725 71.329 1.00 0.00 xxxx 765 ATOM 766 N TYR A 102 99.187 7.595 68.740 1.00 0.00 xxxx 766 ATOM 767 CA TYR A 102 100.022 6.395 68.694 1.00 0.00 xxxx 767 ATOM 768 C TYR A 102 99.397 5.398 67.737 1.00 0.00 xxxx 768 ATOM 769 O TYR A 102 98.228 5.037 67.906 1.00 0.00 xxxx 769 ATOM 770 CB TYR A 102 100.154 5.792 70.096 1.00 0.00 xxxx 770 ATOM 771 CG TYR A 102 101.138 4.640 70.265 1.00 0.00 xxxx 771 ATOM 772 CD1 TYR A 102 100.853 3.593 71.138 1.00 0.00 xxxx 772 ATOM 773 CD2 TYR A 102 102.352 4.614 69.596 1.00 0.00 xxxx 773 ATOM 774 CE1 TYR A 102 101.740 2.541 71.330 1.00 0.00 xxxx 774 ATOM 775 CE2 TYR A 102 103.260 3.563 69.780 1.00 0.00 xxxx 775 ATOM 776 CZ TYR A 102 102.941 2.531 70.660 1.00 0.00 xxxx 776 ATOM 777 OH TYR A 102 103.832 1.493 70.862 1.00 0.00 xxxx 777 ATOM 778 N ASP A 103 100.165 4.951 66.739 1.00 0.00 xxxx 778 ATOM 779 CA ASP A 103 99.602 4.085 65.707 1.00 0.00 xxxx 779 ATOM 780 C ASP A 103 99.207 2.719 66.273 1.00 0.00 xxxx 780 ATOM 781 O ASP A 103 98.417 2.008 65.670 1.00 0.00 xxxx 781 ATOM 782 CB ASP A 103 100.573 3.912 64.519 1.00 0.00 xxxx 782 ATOM 783 CG ASP A 103 101.943 3.400 64.934 1.00 0.00 xxxx 783 ATOM 784 OD1 ASP A 103 102.138 3.062 66.120 1.00 0.00 xxxx 784 ATOM 785 OD2 ASP A 103 102.834 3.328 64.057 1.00 0.00 xxxx 785 ATOM 786 N LYS A 104 99.732 2.361 67.440 1.00 0.00 xxxx 786 ATOM 787 CA LYS A 104 99.415 1.066 68.020 1.00 0.00 xxxx 787 ATOM 788 C LYS A 104 98.553 1.168 69.286 1.00 0.00 xxxx 788 ATOM 789 O LYS A 104 98.544 0.235 70.094 1.00 0.00 xxxx 789 ATOM 790 CB LYS A 104 100.710 0.295 68.321 1.00 0.00 xxxx 790 ATOM 791 CG LYS A 104 101.487 −0.125 67.063 1.00 0.00 xxxx 791 ATOM 792 CD LYS A 104 102.803 −0.812 67.409 1.00 0.00 xxxx 792 ATOM 793 CE LYS A 104 103.833 0.175 67.931 1.00 0.00 xxxx 793 ATOM 794 NZ LYS A 104 104.492 0.950 66.837 1.00 0.00 xxxx 794 ATOM 795 N ALA A 105 97.822 2.277 69.446 1.00 0.00 xxxx 795 ATOM 796 CA ALA A 105 96.825 2.410 70.515 1.00 0.00 xxxx 796 ATOM 797 C ALA A 105 95.419 2.078 70.019 1.00 0.00 xxxx 797 ATOM 798 O ALA A 105 95.012 2.542 68.957 1.00 0.00 xxxx 798 ATOM 799 CB ALA A 105 96.852 3.822 71.107 1.00 0.00 xxxx 799 ATOM 800 N TYR A 106 94.685 1.279 70.797 1.00 0.00 xxxx 800 ATOM 801 CA TYR A 106 93.312 0.880 70.483 1.00 0.00 xxxx 801 ATOM 802 C TYR A 106 92.440 1.016 71.729 1.00 0.00 xxxx 802 ATOM 803 O TYR A 106 92.966 1.198 72.826 1.00 0.00 xxxx 803 ATOM 804 CB TYR A 106 93.268 −0.567 69.975 1.00 0.00 xxxx 804 ATOM 805 CG TYR A 106 93.943 −0.752 68.640 1.00 0.00 xxxx 805 ATOM 806 CD1 TYR A 106 93.197 −0.796 67.479 1.00 0.00 xxxx 806 ATOM 807 CD2 TYR A 106 95.323 −0.852 68.546 1.00 0.00 xxxx 807 ATOM 808 CE1 TYR A 106 93.807 −0.942 66.245 1.00 0.00 xxxx 808 ATOM 809 CE2 TYR A 106 95.945 −1.003 67.320 1.00 0.00 xxxx 809 ATOM 810 CZ TYR A 106 95.180 −1.045 66.181 1.00 0.00 xxxx 810 ATOM 811 OH TYR A 106 95.776 −1.190 64.941 1.00 0.00 xxxx 811 ATOM 812 N TYR A 107 91.120 0.911 71.562 1.00 0.00 xxxx 812 ATOM 813 CA TYR A 107 90.212 0.931 72.709 1.00 0.00 xxxx 813 ATOM 814 C TYR A 107 89.090 −0.082 72.540 1.00 0.00 xxxx 814 ATOM 815 O TYR A 107 88.493 −0.173 71.477 1.00 0.00 xxxx 815 ATOM 816 CB TYR A 107 89.587 2.325 72.927 1.00 0.00 xxxx 816 ATOM 817 CG TYR A 107 88.629 2.324 74.109 1.00 0.00 xxxx 817 ATOM 818 CD1 TYR A 107 89.110 2.165 75.405 1.00 0.00 xxxx 818 ATOM 819 CD2 TYR A 107 87.255 2.445 73.935 1.00 0.00 xxxx 819 ATOM 820 CE1 TYR A 107 88.257 2.135 76.488 1.00 0.00 xxxx 820 ATOM 821 CE2 TYR A 107 86.387 2.414 75.024 1.00 0.00 xxxx 821 ATOM 822 CZ TYR A 107 86.906 2.261 76.297 1.00 0.00 xxxx 822 ATOM 823 OH TYR A 107 86.058 2.217 77.383 1.00 0.00 xxxx 823 ATOM 824 N VAL A 108 88.797 −0.817 73.612 1.00 0.00 xxxx 824 ATOM 825 CA VAL A 108 87.650 −1.721 73.661 1.00 0.00 xxxx 825 ATOM 826 C VAL A 108 86.720 −1.294 74.784 1.00 0.00 xxxx 826 ATOM 827 O VAL A 108 87.141 −1.184 75.934 1.00 0.00 xxxx 827 ATOM 828 CB VAL A 108 88.087 −3.174 73.877 1.00 0.00 xxxx 828 ATOM 829 CG1 VAL A 108 86.848 −4.086 74.051 1.00 0.00 xxxx 829 ATOM 830 CG2 VAL A 108 88.972 −3.674 72.718 1.00 0.00 xxxx 830 ATOM 831 N GLY A 109 85.460 −1.060 74.457 1.00 0.00 xxxx 831 ATOM 832 CA GLY A 109 84.492 −0.672 75.470 1.00 0.00 xxxx 832 ATOM 833 C GLY A 109 83.079 −0.729 74.934 1.00 0.00 xxxx 833 ATOM 834 O GLY A 109 82.682 −1.717 74.321 1.00 0.00 xxxx 834 ATOM 835 N THR A 110 82.328 0.335 75.196 1.00 0.00 xxxx 835 ATOM 836 CA THR A 110 80.915 0.410 74.843 1.00 0.00 xxxx 836 ATOM 837 C THR A 110 80.556 1.792 74.323 1.00 0.00 xxxx 837 ATOM 838 O THR A 110 81.343 2.734 74.442 1.00 0.00 xxxx 838 ATOM 839 CB THR A 110 80.007 0.132 76.056 1.00 0.00 xxxx 839 ATOM 840 OG1 THR A 110 80.096 1.231 76.975 1.00 0.00 xxxx 840 ATOM 841 CG2 THR A 110 80.418 −1.153 76.784 1.00 0.00 xxxx 841 ATOM 842 N ASP A 111 79.354 1.912 73.755 1.00 0.00 xxxx 842 ATOM 843 CA ASP A 111 78.733 3.209 73.500 1.00 0.00 xxxx 843 ATOM 844 C ASP A 111 77.968 3.609 74.757 1.00 0.00 xxxx 844 ATOM 845 O ASP A 111 76.852 3.152 74.977 1.00 0.00 xxxx 845 ATOM 846 CB ASP A 111 77.803 3.122 72.295 1.00 0.00 xxxx 846 ATOM 847 CG ASP A 111 77.151 4.443 71.945 1.00 0.00 xxxx 847 ATOM 848 OD1 ASP A 111 77.546 5.492 72.494 1.00 0.00 xxxx 848 ATOM 849 OD2 ASP A 111 76.245 4.423 71.089 1.00 0.00 xxxx 849 ATOM 850 N SER A 112 78.584 4.441 75.593 1.00 0.00 xxxx 850 ATOM 851 CA SER A 112 78.050 4.710 76.928 1.00 0.00 xxxx 851 ATOM 852 C SER A 112 76.588 5.181 76.924 1.00 0.00 xxxx 852 ATOM 853 O SER A 112 75.783 4.735 77.743 1.00 0.00 xxxx 853 ATOM 854 CB SER A 112 78.938 5.743 77.632 1.00 0.00 xxxx 854 ATOM 855 OG SER A 112 80.282 5.273 77.722 1.00 0.00 xxxx 855 ATOM 856 N LYS A 113 76.241 6.053 75.980 1.00 0.00 xxxx 856 ATOM 857 CA LYS A 113 74.895 6.620 75.943 1.00 0.00 xxxx 857 ATOM 858 C LYS A 113 73.836 5.534 75.701 1.00 0.00 xxxx 858 ATOM 859 O LYS A 113 72.714 5.640 76.197 1.00 0.00 xxxx 859 ATOM 860 CB LYS A 113 74.799 7.711 74.877 1.00 0.00 xxxx 860 ATOM 861 CG LYS A 113 74.780 7.203 73.457 1.00 0.00 xxxx 861 ATOM 862 CD LYS A 113 74.286 8.278 72.499 1.00 0.00 xxxx 862 ATOM 863 CE LYS A 113 74.040 7.701 71.113 1.00 0.00 xxxx 863 ATOM 864 NZ LYS A 113 75.238 6.994 70.575 1.00 0.00 xxxx 864 ATOM 865 N GLU A 114 74.207 4.479 74.975 1.00 0.00 xxxx 865 ATOM 866 CA GLU A 114 73.270 3.394 74.699 1.00 0.00 xxxx 866 ATOM 867 C GLU A 114 72.725 2.781 75.978 1.00 0.00 xxxx 867 ATOM 868 O GLU A 114 71.543 2.448 76.065 1.00 0.00 xxxx 868 ATOM 869 CB GLU A 114 73.926 2.311 73.843 1.00 0.00 xxxx 869 ATOM 870 CG GLU A 114 72.990 1.167 73.486 1.00 0.00 xxxx 870 ATOM 871 CD GLU A 114 73.671 0.061 72.706 1.00 0.00 xxxx 871 ATOM 872 OE1 GLU A 114 74.705 −0.457 73.172 1.00 0.00 xxxx 872 ATOM 873 OE2 GLU A 114 73.176 −0.290 71.615 1.00 0.00 xxxx 873 ATOM 874 N SER A 115 73.574 2.631 76.987 1.00 0.00 xxxx 874 ATOM 875 CA SER A 115 73.103 2.025 78.228 1.00 0.00 xxxx 875 ATOM 876 C SER A 115 72.096 2.924 78.953 1.00 0.00 xxxx 876 ATOM 877 O SER A 115 71.162 2.423 79.559 1.00 0.00 xxxx 877 ATOM 878 CB SER A 115 74.274 1.673 79.162 1.00 0.00 xxxx 878 ATOM 879 OG SER A 115 75.073 2.791 79.501 1.00 0.00 xxxx 879 ATOM 880 N GLY A 116 72.282 4.240 78.880 1.00 0.00 xxxx 880 ATOM 881 CA GLY A 116 71.305 5.160 79.446 1.00 0.00 xxxx 881 ATOM 882 C GLY A 116 69.965 5.122 78.724 1.00 0.00 xxxx 882 ATOM 883 O GLY A 116 68.903 5.120 79.354 1.00 0.00 xxxx 883 ATOM 884 N ILE A 117 70.015 5.109 77.396 1.00 0.00 xxxx 884 ATOM 885 CA ILE A 117 68.807 5.008 76.584 1.00 0.00 xxxx 885 ATOM 886 C ILE A 117 68.071 3.700 76.894 1.00 0.00 xxxx 886 ATOM 887 O ILE A 117 66.856 3.699 77.111 1.00 0.00 xxxx 887 ATOM 888 CB ILE A 117 69.147 5.119 75.093 1.00 0.00 xxxx 888 ATOM 889 CG2 ILE A 117 67.908 4.856 74.240 1.00 0.00 xxxx 889 ATOM 890 CG1 ILE A 117 69.742 6.498 74.792 1.00 0.00 xxxx 890 ATOM 891 CD1 ILE A 117 70.257 6.656 73.391 1.00 0.00 xxxx 891 ATOM 892 N ILE A 118 68.800 2.586 76.914 1.00 0.00 xxxx 892 ATOM 893 CA ILE A 118 68.164 1.304 77.208 1.00 0.00 xxxx 893 ATOM 894 C ILE A 118 67.565 1.302 78.609 1.00 0.00 xxxx 894 ATOM 895 O ILE A 118 66.458 0.799 78.810 1.00 0.00 xxxx 895 ATOM 896 CB ILE A 118 69.142 0.147 77.015 1.00 0.00 xxxx 896 ATOM 897 CG1 ILE A 118 69.483 0.027 75.528 1.00 0.00 xxxx 897 ATOM 898 CG2 ILE A 118 68.535 −1.155 77.531 1.00 0.00 xxxx 898 ATOM 899 CD1 ILE A 118 70.562 −1.000 75.227 1.00 0.00 xxxx 899 ATOM 900 N GLN A 119 68.272 1.879 79.579 1.00 0.00 xxxx 900 ATOM 901 CA GLN A 119 67.736 1.916 80.932 1.00 0.00 xxxx 901 ATOM 902 C GLN A 119 66.448 2.738 80.996 1.00 0.00 xxxx 902 ATOM 903 O GLN A 119 65.490 2.339 81.649 1.00 0.00 xxxx 903 ATOM 904 CB GLN A 119 68.773 2.472 81.915 1.00 0.00 xxxx 904 ATOM 905 CG GLN A 119 68.356 2.257 83.375 1.00 0.00 xxxx 905 ATOM 906 CD GLN A 119 69.334 2.890 84.345 1.00 0.00 xxxx 906 ATOM 907 OE1 GLN A 119 69.729 4.042 84.172 1.00 0.00 xxxx 907 ATOM 908 NE2 GLN A 119 69.722 2.145 85.371 1.00 0.00 xxxx 908 ATOM 909 N GLY A 120 66.422 3.866 80.296 1.00 0.00 xxxx 909 ATOM 910 CA GLY A 120 65.229 4.697 80.240 1.00 0.00 xxxx 910 ATOM 911 C GLY A 120 64.057 3.986 79.584 1.00 0.00 xxxx 911 ATOM 912 O GLY A 120 62.917 4.111 80.032 1.00 0.00 xxxx 912 ATOM 913 N ASP A 121 64.323 3.268 78.502 1.00 0.00 xxxx 913 ATOM 914 CA ASP A 121 63.258 2.583 77.780 1.00 0.00 xxxx 914 ATOM 915 C ASP A 121 62.695 1.453 78.634 1.00 0.00 xxxx 915 ATOM 916 O ASP A 121 61.505 1.142 78.573 1.00 0.00 xxxx 916 ATOM 917 CB ASP A 121 63.779 2.051 76.446 1.00 0.00 xxxx 917 ATOM 918 CG ASP A 121 62.776 1.169 75.740 1.00 0.00 xxxx 918 ATOM 919 OD1 ASP A 121 61.896 1.712 75.040 1.00 0.00 xxxx 919 ATOM 920 OD2 ASP A 121 62.875 −0.068 75.881 1.00 0.00 xxxx 920 ATOM 921 N LEU A 122 63.564 0.857 79.444 1.00 0.00 xxxx 921 ATOM 922 CA LEU A 122 63.166 −0.201 80.362 1.00 0.00 xxxx 922 ATOM 923 C LEU A 122 62.257 0.340 81.468 1.00 0.00 xxxx 923 ATOM 924 O LEU A 122 61.190 −0.218 81.734 1.00 0.00 xxxx 924 ATOM 925 CB LEU A 122 64.407 −0.866 80.964 1.00 0.00 xxxx 925 ATOM 926 CG LEU A 122 64.182 −2.202 81.667 1.00 0.00 xxxx 926 ATOM 927 CD1 LEU A 122 63.510 −3.183 80.713 1.00 0.00 xxxx 927 ATOM 928 CD2 LEU A 122 65.509 −2.750 82.177 1.00 0.00 xxxx 928 ATOM 929 N ILE A 123 62.684 1.429 82.108 1.00 0.00 xxxx 929 ATOM 930 CA ILE A 123 61.890 2.097 83.132 1.00 0.00 xxxx 930 ATOM 931 C ILE A 123 60.524 2.474 82.561 1.00 0.00 xxxx 931 ATOM 932 O ILE A 123 59.499 2.260 83.206 1.00 0.00 xxxx 932 ATOM 933 CB ILE A 123 62.622 3.325 83.692 1.00 0.00 xxxx 933 ATOM 934 CG1 ILE A 123 63.881 2.881 84.437 1.00 0.00 xxxx 934 ATOM 935 CG2 ILE A 123 61.692 4.122 84.624 1.00 0.00 xxxx 935 ATOM 936 CD1 ILE A 123 64.782 4.037 84.868 1.00 0.00 xxxx 936 ATOM 937 N ALA A 124 60.501 3.010 81.346 1.00 0.00 xxxx 937 ATOM 938 CA ALA A 124 59.229 3.381 80.715 1.00 0.00 xxxx 938 ATOM 939 C ALA A 124 58.288 2.187 80.553 1.00 0.00 xxxx 939 ATOM 940 O ALA A 124 57.078 2.294 80.797 1.00 0.00 xxxx 940 ATOM 941 CB ALA A 124 59.483 4.037 79.367 1.00 0.00 xxxx 941 ATOM 942 N LYS A 125 58.845 1.052 80.141 1.00 0.00 xxxx 942 ATOM 943 CA LYS A 125 58.071 −0.168 79.945 1.00 0.00 xxxx 943 ATOM 944 C LYS A 125 57.428 −0.619 81.251 1.00 0.00 xxxx 944 ATOM 945 O LYS A 125 56.235 −0.954 81.296 1.00 0.00 xxxx 945 ATOM 946 CB LYS A 125 58.978 −1.267 79.381 1.00 0.00 xxxx 946 ATOM 947 CG LYS A 125 58.334 −2.651 79.292 1.00 0.00 xxxx 947 ATOM 948 CD LYS A 125 59.409 −3.705 79.021 1.00 0.00 xxxx 948 ATOM 949 CE LYS A 125 58.828 −5.103 79.036 1.00 0.00 xxxx 949 ATOM 950 NZ LYS A 125 59.892 −6.128 78.877 1.00 0.00 xxxx 950 ATOM 951 N HIS A 126 58.221 −0.622 82.320 1.00 0.00 xxxx 951 ATOM 952 CA HIS A 126 57.741 −1.131 83.596 1.00 0.00 xxxx 952 ATOM 953 C HIS A 126 56.831 −0.138 84.296 1.00 0.00 xxxx 953 ATOM 954 O HIS A 126 55.894 −0.543 84.980 1.00 0.00 xxxx 954 ATOM 955 CB HIS A 126 58.922 −1.523 84.478 1.00 0.00 xxxx 955 ATOM 956 CG HIS A 126 59.593 −2.778 84.016 1.00 0.00 xxxx 956 ATOM 957 ND1 HIS A 126 59.266 −4.020 84.514 1.00 0.00 xxxx 957 ATOM 958 CD2 HIS A 126 60.510 −2.990 83.041 1.00 0.00 xxxx 958 ATOM 959 CE1 HIS A 126 59.983 −4.943 83.893 1.00 0.00 xxxx 959 ATOM 960 NE2 HIS A 126 60.744 −4.343 82.995 1.00 0.00 xxxx 960 ATOM 961 N TRP A 127 57.089 1.154 84.103 1.00 0.00 xxxx 961 ATOM 962 CA TRP A 127 56.206 2.213 84.605 1.00 0.00 xxxx 962 ATOM 963 C TRP A 127 54.805 2.083 84.022 1.00 0.00 xxxx 963 ATOM 964 O TRP A 127 53.803 2.171 84.746 1.00 0.00 xxxx 964 ATOM 965 CB TRP A 127 56.807 3.583 84.262 1.00 0.00 xxxx 965 ATOM 966 CG TRP A 127 56.008 4.805 84.674 1.00 0.00 xxxx 966 ATOM 967 CD1 TRP A 127 55.272 5.607 83.854 1.00 0.00 xxxx 967 ATOM 968 CD2 TRP A 127 55.927 5.383 85.982 1.00 0.00 xxxx 968 ATOM 969 NE1 TRP A 127 54.716 6.642 84.574 1.00 0.00 xxxx 969 ATOM 970 CE2 TRP A 127 55.110 6.527 85.882 1.00 0.00 xxxx 970 ATOM 971 CE3 TRP A 127 56.469 5.045 87.229 1.00 0.00 xxxx 971 ATOM 972 CZ2 TRP A 127 54.818 7.335 86.982 1.00 0.00 xxxx 972 ATOM 973 CZ3 TRP A 127 56.183 5.849 88.320 1.00 0.00 xxxx 973 ATOM 974 CH2 TRP A 127 55.360 6.980 88.191 1.00 0.00 xxxx 974 ATOM 975 N ALA A 128 54.730 1.869 82.713 1.00 0.00 xxxx 975 ATOM 976 CA ALA A 128 53.439 1.684 82.051 1.00 0.00 xxxx 976 ATOM 977 C ALA A 128 52.691 0.465 82.606 1.00 0.00 xxxx 977 ATOM 978 O ALA A 128 51.459 0.480 82.734 1.00 0.00 xxxx 978 ATOM 979 CB ALA A 128 53.635 1.546 80.545 1.00 0.00 xxxx 979 ATOM 980 N ALA A 129 53.438 −0.580 82.946 1.00 0.00 xxxx 980 ATOM 981 CA ALA A 129 52.859 −1.837 83.413 1.00 0.00 xxxx 981 ATOM 982 C ALA A 129 52.549 −1.841 84.911 1.00 0.00 xxxx 982 ATOM 983 O ALA A 129 51.876 −2.744 85.401 1.00 0.00 xxxx 983 ATOM 984 CB ALA A 129 53.793 −2.995 83.084 1.00 0.00 xxxx 984 ATOM 985 N ASN A 130 53.053 −0.847 85.636 1.00 0.00 xxxx 985 ATOM 986 CA ASN A 130 52.878 −0.801 87.086 1.00 0.00 xxxx 986 ATOM 987 C ASN A 130 52.454 0.593 87.527 1.00 0.00 xxxx 987 ATOM 988 O ASN A 130 53.226 1.290 88.173 1.00 0.00 xxxx 988 ATOM 989 CB ASN A 130 54.179 −1.189 87.808 1.00 0.00 xxxx 989 ATOM 990 CG ASN A 130 54.592 −2.629 87.551 1.00 0.00 xxxx 990 ATOM 991 OD1 ASN A 130 54.189 −3.538 88.283 1.00 0.00 xxxx 991 ATOM 992 ND2 ASN A 130 55.397 −2.847 86.509 1.00 0.00 xxxx 992 ATOM 993 N GLN A 131 51.236 1.005 87.192 1.00 0.00 xxxx 993 ATOM 994 CA GLN A 131 50.836 2.377 87.493 1.00 0.00 xxxx 994 ATOM 995 C GLN A 131 50.664 2.616 88.994 1.00 0.00 xxxx 995 ATOM 996 O GLN A 131 50.591 3.756 89.434 1.00 0.00 xxxx 996 ATOM 997 CB GLN A 131 49.558 2.737 86.743 1.00 0.00 xxxx 997 ATOM 998 CG GLN A 131 49.811 3.113 85.287 1.00 0.00 xxxx 998 ATOM 999 CD GLN A 131 50.666 4.365 85.145 1.00 0.00 xxxx 999 ATOM 1000 OE1 GLN A 131 50.176 5.486 85.303 1.00 0.00 xxxx 1000 ATOM 1001 NE2 GLN A 131 51.949 4.180 84.848 1.00 0.00 xxxx 1001 ATOM 1002 N GLY A 132 50.627 1.541 89.773 1.00 0.00 xxxx 1002 ATOM 1003 CA GLY A 132 50.664 1.661 91.218 1.00 0.00 xxxx 1003 ATOM 1004 C GLY A 132 51.957 2.255 91.741 1.00 0.00 xxxx 1004 ATOM 1005 O GLY A 132 52.014 2.708 92.886 1.00 0.00 xxxx 1005 ATOM 1006 N TRP A 133 52.999 2.266 90.906 1.00 0.00 xxxx 1006 ATOM 1007 CA TRP A 133 54.265 2.885 91.281 1.00 0.00 xxxx 1007 ATOM 1008 C TRP A 133 54.179 4.410 91.375 1.00 0.00 xxxx 1008 ATOM 1009 O TRP A 133 55.021 5.042 92.004 1.00 0.00 xxxx 1009 ATOM 1010 CB TRP A 133 55.369 2.526 90.279 1.00 0.00 xxxx 1010 ATOM 1011 CG TRP A 133 55.859 1.107 90.312 1.00 0.00 xxxx 1011 ATOM 1012 CD1 TRP A 133 55.501 0.119 91.186 1.00 0.00 xxxx 1012 ATOM 1013 CD2 TRP A 133 56.818 0.531 89.423 1.00 0.00 xxxx 1013 ATOM 1014 NE1 TRP A 133 56.190 −1.045 90.890 1.00 0.00 xxxx 1014 ATOM 1015 CE2 TRP A 133 56.997 −0.816 89.806 1.00 0.00 xxxx 1015 ATOM 1016 CE3 TRP A 133 57.544 1.025 88.334 1.00 0.00 xxxx 1016 ATOM 1017 CZ2 TRP A 133 57.877 −1.674 89.140 1.00 0.00 xxxx 1017 ATOM 1018 CZ3 TRP A 133 58.422 0.170 87.671 1.00 0.00 xxxx 1018 ATOM 1019 CH2 TRP A 133 58.574 −1.165 88.079 1.00 0.00 xxxx 1019 ATOM 1020 N ASP A 134 53.175 4.985 90.714 1.00 0.00 xxxx 1020 ATOM 1021 CA ASP A 134 52.940 6.423 90.756 1.00 0.00 xxxx 1021 ATOM 1022 C ASP A 134 52.241 6.760 92.070 1.00 0.00 xxxx 1022 ATOM 1023 O ASP A 134 51.022 6.966 92.112 1.00 0.00 xxxx 1023 ATOM 1024 CB ASP A 134 52.105 6.842 89.543 1.00 0.00 xxxx 1024 ATOM 1025 CG ASP A 134 51.978 8.350 89.382 1.00 0.00 xxxx 1025 ATOM 1026 OD1 ASP A 134 52.701 9.111 90.044 1.00 0.00 xxxx 1026 ATOM 1027 OD2 ASP A 134 51.151 8.771 88.554 1.00 0.00 xxxx 1027 ATOM 1028 N LEU A 135 53.031 6.800 93.141 1.00 0.00 xxxx 1028 ATOM 1029 CA LEU A 135 52.494 6.901 94.496 1.00 0.00 xxxx 1029 ATOM 1030 C LEU A 135 51.661 8.154 94.723 1.00 0.00 xxxx 1030 ATOM 1031 O LEU A 135 50.639 8.093 95.418 1.00 0.00 xxxx 1031 ATOM 1032 CB LEU A 135 53.636 6.852 95.513 1.00 0.00 xxxx 1032 ATOM 1033 CG LEU A 135 54.522 5.609 95.486 1.00 0.00 xxxx 1033 ATOM 1034 CD1 LEU A 135 55.586 5.739 96.573 1.00 0.00 xxxx 1034 ATOM 1035 CD2 LEU A 135 53.695 4.365 95.696 1.00 0.00 xxxx 1035 ATOM 1036 N ASN A 136 52.068 9.286 94.148 1.00 0.00 xxxx 1036 ATOM 1037 CA ASN A 136 51.282 10.512 94.345 1.00 0.00 xxxx 1037 ATOM 1038 C ASN A 136 50.294 10.778 93.208 1.00 0.00 xxxx 1038 ATOM 1039 O ASN A 136 49.642 11.827 93.183 1.00 0.00 xxxx 1039 ATOM 1040 CB ASN A 136 52.193 11.729 94.543 1.00 0.00 xxxx 1040 ATOM 1041 CG ASN A 136 52.931 12.144 93.274 1.00 0.00 xxxx 1041 ATOM 1042 OD1 ASN A 136 53.028 11.386 92.307 1.00 0.00 xxxx 1042 ATOM 1043 ND2 ASN A 136 53.477 13.362 93.289 1.00 0.00 xxxx 1043 ATOM 1044 N LYS A 137 50.197 9.830 92.280 1.00 0.00 xxxx 1044 ATOM 1045 CA LYS A 137 49.160 9.856 91.239 1.00 0.00 xxxx 1045 ATOM 1046 C LYS A 137 49.225 11.109 90.363 1.00 0.00 xxxx 1046 ATOM 1047 O LYS A 137 48.189 11.578 89.883 1.00 0.00 xxxx 1047 ATOM 1048 CB LYS A 137 47.770 9.736 91.883 1.00 0.00 xxxx 1048 ATOM 1049 CG LYS A 137 47.571 8.425 92.630 1.00 0.00 xxxx 1049 ATOM 1050 CD LYS A 137 46.208 8.359 93.303 1.00 0.00 xxxx 1050 ATOM 1051 CE LYS A 137 45.091 8.308 92.284 1.00 0.00 xxxx 1051 ATOM 1052 NZ LYS A 137 45.115 7.052 91.487 1.00 0.00 xxxx 1052 ATOM 1053 N ASP A 138 50.428 11.638 90.135 1.00 0.00 xxxx 1053 ATOM 1054 CA ASP A 138 50.554 12.869 89.344 1.00 0.00 xxxx 1054 ATOM 1055 C ASP A 138 51.009 12.636 87.901 1.00 0.00 xxxx 1055 ATOM 1056 O ASP A 138 51.184 13.594 87.148 1.00 0.00 xxxx 1056 ATOM 1057 CB ASP A 138 51.499 13.865 90.041 1.00 0.00 xxxx 1057 ATOM 1058 CG ASP A 138 52.965 13.447 90.011 1.00 0.00 xxxx 1058 ATOM 1059 OD1 ASP A 138 53.285 12.308 89.603 1.00 0.00 xxxx 1059 ATOM 1060 OD2 ASP A 138 53.812 14.281 90.431 1.00 0.00 xxxx 1060 ATOM 1061 N GLY A 139 51.196 11.374 87.519 1.00 0.00 xxxx 1061 ATOM 1062 CA GLY A 139 51.634 11.030 86.174 1.00 0.00 xxxx 1062 ATOM 1063 C GLY A 139 53.104 11.282 85.887 1.00 0.00 xxxx 1063 ATOM 1064 O GLY A 139 53.555 11.086 84.757 1.00 0.00 xxxx 1064 ATOM 1065 N GLN A 140 53.859 11.686 86.910 1.00 0.00 xxxx 1065 ATOM 1066 CA GLN A 140 55.299 11.929 86.779 1.00 0.00 xxxx 1066 ATOM 1067 C GLN A 140 56.057 10.927 87.603 1.00 0.00 xxxx 1067 ATOM 1068 O GLN A 140 55.531 10.447 88.612 1.00 0.00 xxxx 1068 ATOM 1069 CB GLN A 140 55.682 13.327 87.258 1.00 0.00 xxxx 1069 ATOM 1070 CG GLN A 140 54.808 14.436 86.722 1.00 0.00 xxxx 1070 ATOM 1071 CD GLN A 140 55.319 15.804 87.115 1.00 0.00 xxxx 1071 ATOM 1072 OE1 GLN A 140 56.517 15.992 87.328 1.00 0.00 xxxx 1072 ATOM 1073 NE2 GLN A 140 54.412 16.769 87.222 1.00 0.00 xxxx 1073 ATOM 1074 N ILE A 141 57.275 10.594 87.178 1.00 0.00 xxxx 1074 ATOM 1075 CA ILE A 141 58.146 9.760 88.003 1.00 0.00 xxxx 1075 ATOM 1076 C ILE A 141 58.978 10.606 88.964 1.00 0.00 xxxx 1076 ATOM 1077 O ILE A 141 59.856 11.347 88.538 1.00 0.00 xxxx 1077 ATOM 1078 CB ILE A 141 59.090 8.899 87.162 1.00 0.00 xxxx 1078 ATOM 1079 CG1 ILE A 141 58.300 7.990 86.223 1.00 0.00 xxxx 1079 ATOM 1080 CD1 ILE A 141 59.209 7.121 85.330 1.00 0.00 xxxx 1080 ATOM 1081 CG2 ILE A 141 60.002 8.087 88.090 1.00 0.00 xxxx 1081 ATOM 1082 N GLN A 142 58.695 10.497 90.256 1.00 0.00 xxxx 1082 ATOM 1083 CA GLN A 142 59.568 11.073 91.274 1.00 0.00 xxxx 1083 ATOM 1084 C GLN A 142 60.693 10.084 91.528 1.00 0.00 xxxx 1084 ATOM 1085 O GLN A 142 60.453 8.970 92.000 1.00 0.00 xxxx 1085 ATOM 1086 CB GLN A 142 58.795 11.361 92.562 1.00 0.00 xxxx 1086 ATOM 1087 CG GLN A 142 58.111 12.718 92.607 1.00 0.00 xxxx 1087 ATOM 1088 CD GLN A 142 56.877 12.796 91.716 1.00 0.00 xxxx 1088 ATOM 1089 OE1 GLN A 142 56.161 11.805 91.524 1.00 0.00 xxxx 1089 ATOM 1090 NE2 GLN A 142 56.611 13.987 91.190 1.00 0.00 xxxx 1090 ATOM 1091 N PHE A 143 61.916 10.468 91.183 1.00 0.00 xxxx 1091 ATOM 1092 CA PHE A 143 63.031 9.530 91.267 1.00 0.00 xxxx 1092 ATOM 1093 C PHE A 143 64.180 10.041 92.119 1.00 0.00 xxxx 1093 ATOM 1094 O PHE A 143 64.290 11.237 92.391 1.00 0.00 xxxx 1094 ATOM 1095 CB PHE A 143 63.561 9.192 89.856 1.00 0.00 xxxx 1095 ATOM 1096 CG PHE A 143 64.318 10.321 89.187 1.00 0.00 xxxx 1096 ATOM 1097 CD1 PHE A 143 65.710 10.383 89.259 1.00 0.00 xxxx 1097 ATOM 1098 CD2 PHE A 143 63.647 11.301 88.475 1.00 0.00 xxxx 1098 ATOM 1099 CE1 PHE A 143 66.415 11.409 88.638 1.00 0.00 xxxx 1099 ATOM 1100 CE2 PHE A 143 64.342 12.332 87.852 1.00 0.00 xxxx 1100 ATOM 1101 CZ PHE A 143 65.730 12.386 87.936 1.00 0.00 xxxx 1101 ATOM 1102 N VAL A 144 65.038 9.116 92.534 1.00 0.00 xxxx 1102 ATOM 1103 CA VAL A 144 66.359 9.480 93.032 1.00 0.00 xxxx 1103 ATOM 1104 C VAL A 144 67.364 8.774 92.143 1.00 0.00 xxxx 1104 ATOM 1105 O VAL A 144 67.052 7.737 91.557 1.00 0.00 xxxx 1105 ATOM 1106 CB VAL A 144 66.579 9.111 94.511 1.00 0.00 xxxx 1106 ATOM 1107 CG1 VAL A 144 65.579 9.852 95.400 1.00 0.00 xxxx 1107 ATOM 1108 CG2 VAL A 144 66.496 7.598 94.726 1.00 0.00 xxxx 1108 ATOM 1109 N LEU A 145 68.556 9.348 92.009 1.00 0.00 xxxx 1109 ATOM 1110 CA LEU A 145 69.551 8.754 91.118 1.00 0.00 xxxx 1110 ATOM 1111 C LEU A 145 70.913 8.649 91.792 1.00 0.00 xxxx 1111 ATOM 1112 O LEU A 145 71.429 9.620 92.348 1.00 0.00 xxxx 1112 ATOM 1113 CB LEU A 145 69.651 9.557 89.808 1.00 0.00 xxxx 1113 ATOM 1114 CG LEU A 145 70.503 8.946 88.676 1.00 0.00 xxxx 1114 ATOM 1115 CD1 LEU A 145 69.943 9.329 87.311 1.00 0.00 xxxx 1115 ATOM 1116 CD2 LEU A 145 71.965 9.353 88.771 1.00 0.00 xxxx 1116 ATOM 1117 N LEU A 146 71.462 7.438 91.735 1.00 0.00 xxxx 1117 ATOM 1118 CA LEU A 146 72.791 7.139 92.259 1.00 0.00 xxxx 1118 ATOM 1119 C LEU A 146 73.792 7.143 91.107 1.00 0.00 xxxx 1119 ATOM 1120 O LEU A 146 73.759 6.267 90.238 1.00 0.00 xxxx 1120 ATOM 1121 CB LEU A 146 72.770 5.788 92.984 1.00 0.00 xxxx 1121 ATOM 1122 CG LEU A 146 71.969 5.854 94.285 1.00 0.00 xxxx 1122 ATOM 1123 CD1 LEU A 146 71.464 4.479 94.688 1.00 0.00 xxxx 1123 ATOM 1124 CD2 LEU A 146 72.845 6.450 95.380 1.00 0.00 xxxx 1124 ATOM 1125 N LYS A 147 74.662 8.147 91.095 1.00 0.00 xxxx 1125 ATOM 1126 CA LYS A 147 75.583 8.361 89.986 1.00 0.00 xxxx 1126 ATOM 1127 C LYS A 147 76.939 7.700 90.244 1.00 0.00 xxxx 1127 ATOM 1128 O LYS A 147 77.365 7.565 91.391 1.00 0.00 xxxx 1128 ATOM 1129 CB LYS A 147 75.739 9.871 89.754 1.00 0.00 xxxx 1129 ATOM 1130 CG LYS A 147 76.634 10.249 88.595 1.00 0.00 xxxx 1130 ATOM 1131 CD LYS A 147 76.509 11.741 88.309 1.00 0.00 xxxx 1131 ATOM 1132 CE LYS A 147 77.457 12.148 87.189 1.00 0.00 xxxx 1132 ATOM 1133 NZ LYS A 147 77.409 13.623 86.951 1.00 0.00 xxxx 1133 ATOM 1134 N GLY A 148 77.607 7.268 89.174 1.00 0.00 xxxx 1134 ATOM 1135 CA GLY A 148 78.973 6.778 89.262 1.00 0.00 xxxx 1135 ATOM 1136 C GLY A 148 80.004 7.876 89.465 1.00 0.00 xxxx 1136 ATOM 1137 O GLY A 148 79.660 8.999 89.844 1.00 0.00 xxxx 1137 ATOM 1138 N GLU A 149 81.269 7.544 89.201 1.00 0.00 xxxx 1138 ATOM 1139 CA GLU A 149 82.387 8.479 89.315 1.00 0.00 xxxx 1139 ATOM 1140 C GLU A 149 82.189 9.673 88.390 1.00 0.00 xxxx 1140 ATOM 1141 O GLU A 149 82.058 9.502 87.185 1.00 0.00 xxxx 1141 ATOM 1142 CB GLU A 149 83.705 7.763 88.982 1.00 0.00 xxxx 1142 ATOM 1143 CG GLU A 149 84.892 8.693 88.733 1.00 0.00 xxxx 1143 ATOM 1144 CD GLU A 149 86.163 7.955 88.312 1.00 0.00 xxxx 1144 ATOM 1145 OE1 GLU A 149 86.160 7.257 87.269 1.00 0.00 xxxx 1145 ATOM 1146 OE2 GLU A 149 87.176 8.078 89.032 1.00 0.00 xxxx 1146 ATOM 1147 N PRO A 150 82.139 10.889 88.954 1.00 0.00 xxxx 1147 ATOM 1148 CA PRO A 150 81.976 12.064 88.090 1.00 0.00 xxxx 1148 ATOM 1149 C PRO A 150 83.076 12.150 87.034 1.00 0.00 xxxx 1149 ATOM 1150 O PRO A 150 84.254 11.966 87.346 1.00 0.00 xxxx 1150 ATOM 1151 CB PRO A 150 82.054 13.233 89.076 1.00 0.00 xxxx 1151 ATOM 1152 CG PRO A 150 81.585 12.636 90.382 1.00 0.00 xxxx 1152 ATOM 1153 CD PRO A 150 82.150 11.246 90.383 1.00 0.00 xxxx 1153 ATOM 1154 N GLY A 151 82.686 12.388 85.786 1.00 0.00 xxxx 1154 ATOM 1155 CA GLY A 151 83.636 12.431 84.690 1.00 0.00 xxxx 1155 ATOM 1156 C GLY A 151 83.867 11.116 83.969 1.00 0.00 xxxx 1156 ATOM 1157 O GLY A 151 84.386 11.100 82.852 1.00 0.00 xxxx 1157 ATOM 1158 N HIS A 152 83.505 10.008 84.610 1.00 0.00 xxxx 1158 ATOM 1159 CA HIS A 152 83.556 8.702 83.962 1.00 0.00 xxxx 1159 ATOM 1160 C HIS A 152 82.542 8.753 82.832 1.00 0.00 xxxx 1160 ATOM 1161 O HIS A 152 81.397 9.117 83.066 1.00 0.00 xxxx 1161 ATOM 1162 CB HIS A 152 83.232 7.586 84.968 1.00 0.00 xxxx 1162 ATOM 1163 CG HIS A 152 83.493 6.196 84.467 1.00 0.00 xxxx 1163 ATOM 1164 ND1 HIS A 152 82.885 5.674 83.345 1.00 0.00 xxxx 1164 ATOM 1165 CD2 HIS A 152 84.270 5.205 84.966 1.00 0.00 xxxx 1165 ATOM 1166 CE1 HIS A 152 83.290 4.429 83.162 1.00 0.00 xxxx 1166 ATOM 1167 NE2 HIS A 152 84.131 4.120 84.134 1.00 0.00 xxxx 1167 ATOM 1168 N PRO A 153 82.963 8.418 81.602 1.00 0.00 xxxx 1168 ATOM 1169 CA PRO A 153 82.057 8.494 80.450 1.00 0.00 xxxx 1169 ATOM 1170 C PRO A 153 80.746 7.753 80.671 1.00 0.00 xxxx 1170 ATOM 1171 O PRO A 153 79.684 8.243 80.282 1.00 0.00 xxxx 1171 ATOM 1172 CB PRO A 153 82.867 7.831 79.330 1.00 0.00 xxxx 1172 ATOM 1173 CG PRO A 153 84.262 8.052 79.713 1.00 0.00 xxxx 1173 ATOM 1174 CD PRO A 153 84.313 7.980 81.209 1.00 0.00 xxxx 1174 ATOM 1175 N ASP A 154 80.818 6.585 81.300 1.00 0.00 xxxx 1175 ATOM 1176 CA ASP A 154 79.619 5.782 81.532 1.00 0.00 xxxx 1176 ATOM 1177 C ASP A 154 78.681 6.459 82.518 1.00 0.00 xxxx 1177 ATOM 1178 O ASP A 154 77.477 6.478 82.308 1.00 0.00 xxxx 1178 ATOM 1179 CB ASP A 154 79.969 4.382 82.041 1.00 0.00 xxxx 1179 ATOM 1180 CG ASP A 154 80.549 3.488 80.956 1.00 0.00 xxxx 1180 ATOM 1181 OD1 ASP A 154 80.282 3.727 79.756 1.00 0.00 xxxx 1181 ATOM 1182 OD2 ASP A 154 81.262 2.524 81.298 1.00 0.00 xxxx 1182 ATOM 1183 N ALA A 155 79.225 6.992 83.609 1.00 0.00 xxxx 1183 ATOM 1184 CA ALA A 155 78.391 7.677 84.597 1.00 0.00 xxxx 1184 ATOM 1185 C ALA A 155 77.702 8.915 84.010 1.00 0.00 xxxx 1185 ATOM 1186 O ALA A 155 76.509 9.131 84.215 1.00 0.00 xxxx 1186 ATOM 1187 CB ALA A 155 79.220 8.067 85.819 1.00 0.00 xxxx 1187 ATOM 1188 N GLU A 156 78.455 9.731 83.276 1.00 0.00 xxxx 1188 ATOM 1189 CA GLU A 156 77.885 10.946 82.720 1.00 0.00 xxxx 1189 ATOM 1190 C GLU A 156 76.799 10.637 81.693 1.00 0.00 xxxx 1190 ATOM 1191 O GLU A 156 75.725 11.221 81.738 1.00 0.00 xxxx 1191 ATOM 1192 CB GLU A 156 78.973 11.814 82.091 1.00 0.00 xxxx 1192 ATOM 1193 CG GLU A 156 80.011 12.322 83.083 1.00 0.00 xxxx 1193 ATOM 1194 CD GLU A 156 79.422 13.168 84.199 1.00 0.00 xxxx 1194 ATOM 1195 OE1 GLU A 156 78.347 13.780 84.009 1.00 0.00 xxxx 1195 ATOM 1196 OE2 GLU A 156 80.049 13.224 85.276 1.00 0.00 xxxx 1196 ATOM 1197 N ALA A 157 77.090 9.729 80.765 1.00 0.00 xxxx 1197 ATOM 1198 CA ALA A 157 76.121 9.347 79.745 1.00 0.00 xxxx 1198 ATOM 1199 C ALA A 157 74.890 8.658 80.332 1.00 0.00 xxxx 1199 ATOM 1200 O ALA A 157 73.761 8.943 79.922 1.00 0.00 xxxx 1200 ATOM 1201 CB ALA A 157 76.775 8.439 78.713 1.00 0.00 xxxx 1201 ATOM 1202 N ARG A 158 75.085 7.754 81.286 1.00 0.00 xxxx 1202 ATOM 1203 CA ARG A 158 73.946 7.028 81.836 1.00 0.00 xxxx 1203 ATOM 1204 C ARG A 158 73.015 7.947 82.600 1.00 0.00 xxxx 1204 ATOM 1205 O ARG A 158 71.795 7.761 82.596 1.00 0.00 xxxx 1205 ATOM 1206 CB ARG A 158 74.413 5.885 82.742 1.00 0.00 xxxx 1206 ATOM 1207 CG ARG A 158 74.963 4.718 81.960 1.00 0.00 xxxx 1207 ATOM 1208 CD ARG A 158 75.686 3.742 82.866 1.00 0.00 xxxx 1208 ATOM 1209 NE ARG A 158 76.454 2.793 82.073 1.00 0.00 xxxx 1209 ATOM 1210 CZ ARG A 158 77.307 1.917 82.597 1.00 0.00 xxxx 1210 ATOM 1211 NH1 ARG A 158 77.475 1.869 83.918 1.00 0.00 xxxx 1211 ATOM 1212 NH2 ARG A 158 78.000 1.104 81.808 1.00 0.00 xxxx 1212 ATOM 1213 N THR A 159 73.595 8.932 83.272 1.00 0.00 xxxx 1213 ATOM 1214 CA THR A 159 72.812 9.858 84.072 1.00 0.00 xxxx 1214 ATOM 1215 C THR A 159 72.016 10.787 83.165 1.00 0.00 xxxx 1215 ATOM 1216 O THR A 159 70.829 11.022 83.385 1.00 0.00 xxxx 1216 ATOM 1217 CB THR A 159 73.723 10.662 85.000 1.00 0.00 xxxx 1217 ATOM 1218 OG1 THR A 159 74.339 9.767 85.931 1.00 0.00 xxxx 1218 ATOM 1219 CG2 THR A 159 72.930 11.692 85.772 1.00 0.00 xxxx 1219 ATOM 1220 N THR A 160 72.673 11.288 82.128 1.00 0.00 xxxx 1220 ATOM 1221 CA THR A 160 72.007 12.189 81.196 1.00 0.00 xxxx 1221 ATOM 1222 C THR A 160 70.915 11.488 80.402 1.00 0.00 xxxx 1222 ATOM 1223 O THR A 160 69.805 12.009 80.263 1.00 0.00 xxxx 1223 ATOM 1224 CB THR A 160 73.011 12.800 80.207 1.00 0.00 xxxx 1224 ATOM 1225 OG1 THR A 160 73.939 13.636 80.914 1.00 0.00 xxxx 1225 ATOM 1226 CG2 THR A 160 72.289 13.625 79.137 1.00 0.00 xxxx 1226 ATOM 1227 N TYR A 161 71.237 10.319 79.853 1.00 0.00 xxxx 1227 ATOM 1228 CA TYR A 161 70.351 9.740 78.847 1.00 0.00 xxxx 1228 ATOM 1229 C TYR A 161 69.210 8.901 79.417 1.00 0.00 xxxx 1229 ATOM 1230 O TYR A 161 68.202 8.711 78.729 1.00 0.00 xxxx 1230 ATOM 1231 CB TYR A 161 71.169 8.925 77.829 1.00 0.00 xxxx 1231 ATOM 1232 CG TYR A 161 71.871 9.815 76.830 1.00 0.00 xxxx 1232 ATOM 1233 CD1 TYR A 161 71.230 10.222 75.669 1.00 0.00 xxxx 1233 ATOM 1234 CD2 TYR A 161 73.154 10.285 77.067 1.00 0.00 xxxx 1234 ATOM 1235 CE1 TYR A 161 71.864 11.051 74.756 1.00 0.00 xxxx 1235 ATOM 1236 CE2 TYR A 161 73.792 11.120 76.162 1.00 0.00 xxxx 1236 ATOM 1237 CZ TYR A 161 73.142 11.496 75.012 1.00 0.00 xxxx 1237 ATOM 1238 OH TYR A 161 73.775 12.323 74.112 1.00 0.00 xxxx 1238 ATOM 1239 N VAL A 162 69.310 8.434 80.659 1.00 0.00 xxxx 1239 ATOM 1240 CA VAL A 162 68.155 7.734 81.220 1.00 0.00 xxxx 1240 ATOM 1241 C VAL A 162 66.970 8.708 81.360 1.00 0.00 xxxx 1241 ATOM 1242 O VAL A 162 65.832 8.370 81.008 1.00 0.00 xxxx 1242 ATOM 1243 CB VAL A 162 68.495 7.027 82.564 1.00 0.00 xxxx 1243 ATOM 1244 CG1 VAL A 162 68.829 8.019 83.681 1.00 0.00 xxxx 1244 ATOM 1245 CG2 VAL A 162 67.339 6.120 82.992 1.00 0.00 xxxx 1245 ATOM 1246 N ILE A 163 67.249 9.926 81.817 1.00 0.00 xxxx 1246 ATOM 1247 CA ILE A 163 66.213 10.941 81.981 1.00 0.00 xxxx 1247 ATOM 1248 C ILE A 163 65.767 11.478 80.631 1.00 0.00 xxxx 1248 ATOM 1249 O ILE A 163 64.561 11.682 80.412 1.00 0.00 xxxx 1249 ATOM 1250 CB ILE A 163 66.702 12.073 82.917 1.00 0.00 xxxx 1250 ATOM 1251 CG1 ILE A 163 67.019 11.507 84.306 1.00 0.00 xxxx 1251 ATOM 1252 CG2 ILE A 163 65.663 13.205 83.013 1.00 0.00 xxxx 1252 ATOM 1253 CD1 ILE A 163 65.913 10.626 84.897 1.00 0.00 xxxx 1253 ATOM 1254 N LYS A 164 66.717 11.716 79.730 1.00 0.00 xxxx 1254 ATOM 1255 CA LYS A 164 66.365 12.228 78.410 1.00 0.00 xxxx 1255 ATOM 1256 C LYS A 164 65.417 11.261 77.700 1.00 0.00 xxxx 1256 ATOM 1257 O LYS A 164 64.434 11.676 77.079 1.00 0.00 xxxx 1257 ATOM 1258 CB LYS A 164 67.619 12.461 77.565 1.00 0.00 xxxx 1258 ATOM 1259 CG LYS A 164 67.313 13.048 76.199 1.00 0.00 xxxx 1259 ATOM 1260 CD LYS A 164 68.579 13.299 75.394 1.00 0.00 xxxx 1260 ATOM 1261 CE LYS A 164 68.249 13.646 73.948 1.00 0.00 xxxx 1261 ATOM 1262 NZ LYS A 164 67.187 14.687 73.850 1.00 0.00 xxxx 1262 ATOM 1263 N GLU A 165 65.703 9.969 77.807 1.00 0.00 xxxx 1263 ATOM 1264 CA GLU A 165 64.888 8.978 77.119 1.00 0.00 xxxx 1264 ATOM 1265 C GLU A 165 63.478 8.925 77.699 1.00 0.00 xxxx 1265 ATOM 1266 O GLU A 165 62.496 8.895 76.948 1.00 0.00 xxxx 1266 ATOM 1267 CB GLU A 165 65.548 7.595 77.174 1.00 0.00 xxxx 1267 ATOM 1268 CG GLU A 165 64.772 6.517 76.425 1.00 0.00 xxxx 1268 ATOM 1269 CD GLU A 165 64.739 6.725 74.909 1.00 0.00 xxxx 1269 ATOM 1270 OE1 GLU A 165 65.462 7.595 74.383 1.00 0.00 xxxx 1270 ATOM 1271 OE2 GLU A 165 63.978 6.001 74.234 1.00 0.00 xxxx 1271 ATOM 1272 N LEU A 166 63.367 8.943 79.024 1.00 0.00 xxxx 1272 ATOM 1273 CA LEU A 166 62.055 8.996 79.661 1.00 0.00 xxxx 1273 ATOM 1274 C LEU A 166 61.286 10.233 79.214 1.00 0.00 xxxx 1274 ATOM 1275 O LEU A 166 60.137 10.134 78.784 1.00 0.00 xxxx 1275 ATOM 1276 CB LEU A 166 62.196 8.980 81.185 1.00 0.00 xxxx 1276 ATOM 1277 CG LEU A 166 62.545 7.614 81.779 1.00 0.00 xxxx 1277 ATOM 1278 CD1 LEU A 166 63.027 7.747 83.220 1.00 0.00 xxxx 1278 ATOM 1279 CD2 LEU A 166 61.331 6.689 81.686 1.00 0.00 xxxx 1279 ATOM 1280 N ASN A 167 61.932 11.393 79.281 1.00 0.00 xxxx 1280 ATOM 1281 CA ASN A 167 61.263 12.636 78.902 1.00 0.00 xxxx 1281 ATOM 1282 C ASN A 167 60.872 12.639 77.421 1.00 0.00 xxxx 1282 ATOM 1283 O ASN A 167 59.788 13.121 77.071 1.00 0.00 xxxx 1283 ATOM 1284 CB ASN A 167 62.147 13.848 79.210 1.00 0.00 xxxx 1284 ATOM 1285 CG ASN A 167 62.376 14.059 80.705 1.00 0.00 xxxx 1285 ATOM 1286 OD1 ASN A 167 61.698 13.473 81.558 1.00 0.00 xxxx 1286 ATOM 1287 ND2 ASN A 167 63.329 14.915 81.024 1.00 0.00 xxxx 1287 ATOM 1288 N ASP A 168 61.730 12.088 76.558 1.00 0.00 xxxx 1288 ATOM 1289 CA ASP A 168 61.453 12.062 75.119 1.00 0.00 xxxx 1289 ATOM 1290 C ASP A 168 60.230 11.206 74.833 1.00 0.00 xxxx 1290 ATOM 1291 O ASP A 168 59.505 11.452 73.863 1.00 0.00 xxxx 1291 ATOM 1292 CB ASP A 168 62.658 11.534 74.332 1.00 0.00 xxxx 1292 ATOM 1293 CG ASP A 168 63.759 12.576 74.153 1.00 0.00 xxxx 1293 ATOM 1294 OD1 ASP A 168 63.522 13.772 74.436 1.00 0.00 xxxx 1294 ATOM 1295 OD2 ASP A 168 64.861 12.194 73.707 1.00 0.00 xxxx 1295 ATOM 1296 N LYS A 169 60.003 10.207 75.685 1.00 0.00 xxxx 1296 ATOM 1297 CA LYS A 169 58.855 9.311 75.552 1.00 0.00 xxxx 1297 ATOM 1298 C LYS A 169 57.585 9.897 76.161 1.00 0.00 xxxx 1298 ATOM 1299 O LYS A 169 56.543 9.243 76.175 1.00 0.00 xxxx 1299 ATOM 1300 CB LYS A 169 59.153 7.958 76.203 1.00 0.00 xxxx 1300 ATOM 1301 CG LYS A 169 60.182 7.127 75.469 1.00 0.00 xxxx 1301 ATOM 1302 CD LYS A 169 60.315 5.756 76.107 1.00 0.00 xxxx 1302 ATOM 1303 CE LYS A 169 60.991 4.783 75.159 1.00 0.00 xxxx 1303 ATOM 1304 NZ LYS A 169 60.305 4.701 73.837 1.00 0.00 xxxx 1304 ATOM 1305 N GLY A 170 57.667 11.127 76.657 1.00 0.00 xxxx 1305 ATOM 1306 CA GLY A 170 56.509 11.790 77.233 1.00 0.00 xxxx 1306 ATOM 1307 C GLY A 170 56.263 11.489 78.698 1.00 0.00 xxxx 1307 ATOM 1308 O GLY A 170 55.179 11.753 79.220 1.00 0.00 xxxx 1308 ATOM 1309 N ILE A 171 57.272 10.945 79.370 1.00 0.00 xxxx 1309 ATOM 1310 CA ILE A 171 57.172 10.698 80.804 1.00 0.00 xxxx 1310 ATOM 1311 C ILE A 171 57.941 11.780 81.540 1.00 0.00 xxxx 1311 ATOM 1312 O ILE A 171 59.177 11.813 81.507 1.00 0.00 xxxx 1312 ATOM 1313 CB ILE A 171 57.683 9.305 81.178 1.00 0.00 xxxx 1313 ATOM 1314 CG1 ILE A 171 56.891 8.229 80.423 1.00 0.00 xxxx 1314 ATOM 1315 CD1 ILE A 171 57.515 6.856 80.496 1.00 0.00 xxxx 1315 ATOM 1316 CG2 ILE A 171 57.608 9.094 82.690 1.00 0.00 xxxx 1316 ATOM 1317 N LYS A 172 57.208 12.683 82.187 1.00 0.00 xxxx 1317 ATOM 1318 CA LYS A 172 57.825 13.718 83.004 1.00 0.00 xxxx 1318 ATOM 1319 C LYS A 172 58.452 13.117 84.241 1.00 0.00 xxxx 1319 ATOM 1320 O LYS A 172 57.946 12.143 84.804 1.00 0.00 xxxx 1320 ATOM 1321 CB LYS A 172 56.805 14.770 83.417 1.00 0.00 xxxx 1321 ATOM 1322 CG LYS A 172 56.199 15.537 82.261 1.00 0.00 xxxx 1322 ATOM 1323 CD LYS A 172 55.181 16.549 82.783 1.00 0.00 xxxx 1323 ATOM 1324 CE LYS A 172 54.534 17.326 81.650 1.00 0.00 xxxx 1324 ATOM 1325 NZ LYS A 172 55.536 18.060 80.827 1.00 0.00 xxxx 1325 ATOM 1326 N THR A 173 59.548 13.723 84.672 1.00 0.00 xxxx 1326 ATOM 1327 CA THR A 173 60.320 13.197 85.792 1.00 0.00 xxxx 1327 ATOM 1328 C THR A 173 60.618 14.325 86.761 1.00 0.00 xxxx 1328 ATOM 1329 O THR A 173 60.759 15.480 86.353 1.00 0.00 xxxx 1329 ATOM 1330 CB THR A 173 61.635 12.548 85.320 1.00 0.00 xxxx 1330 ATOM 1331 OG1 THR A 173 62.379 13.472 84.508 1.00 0.00 xxxx 1331 ATOM 1332 CG2 THR A 173 61.352 11.291 84.503 1.00 0.00 xxxx 1332 ATOM 1333 N GLU A 174 60.673 13.995 88.047 1.00 0.00 xxxx 1333 ATOM 1334 CA GLU A 174 61.057 14.966 89.058 1.00 0.00 xxxx 1334 ATOM 1335 C GLU A 174 62.205 14.408 89.878 1.00 0.00 xxxx 1335 ATOM 1336 O GLU A 174 62.055 13.407 90.580 1.00 0.00 xxxx 1336 ATOM 1337 CB GLU A 174 59.894 15.330 89.985 1.00 0.00 xxxx 1337 ATOM 1338 CG GLU A 174 60.320 16.389 91.020 1.00 0.00 xxxx 1338 ATOM 1339 CD GLU A 174 59.264 16.733 92.064 1.00 0.00 xxxx 1339 ATOM 1340 OE1 GLU A 174 58.196 16.086 92.123 1.00 0.00 xxxx 1340 ATOM 1341 OE2 GLU A 174 59.516 17.671 92.848 1.00 0.00 xxxx 1341 ATOM 1342 N GLN A 175 63.350 15.074 89.787 1.00 0.00 xxxx 1342 ATOM 1343 CA GLN A 175 64.556 14.661 90.510 1.00 0.00 xxxx 1343 ATOM 1344 C GLN A 175 64.469 15.050 91.980 1.00 0.00 xxxx 1344 ATOM 1345 O GLN A 175 64.574 16.234 92.315 1.00 0.00 xxxx 1345 ATOM 1346 CB GLN A 175 65.783 15.304 89.874 1.00 0.00 xxxx 1346 ATOM 1347 CG GLN A 175 67.103 14.879 90.484 1.00 0.00 xxxx 1347 ATOM 1348 CD GLN A 175 68.250 15.684 89.923 1.00 0.00 xxxx 1348 ATOM 1349 OE1 GLN A 175 68.903 16.442 90.641 1.00 0.00 xxxx 1349 ATOM 1350 NE2 GLN A 175 68.483 15.545 88.629 1.00 0.00 xxxx 1350 ATOM 1351 N LEU A 176 64.262 14.067 92.850 1.00 0.00 xxxx 1351 ATOM 1352 CA LEU A 176 64.183 14.350 94.293 1.00 0.00 xxxx 1352 ATOM 1353 C LEU A 176 65.546 14.387 94.955 1.00 0.00 xxxx 1353 ATOM 1354 O LEU A 176 65.767 15.180 95.866 1.00 0.00 xxxx 1354 ATOM 1355 CB LEU A 176 63.312 13.305 94.999 1.00 0.00 xxxx 1355 ATOM 1356 CG LEU A 176 61.856 13.217 94.549 1.00 0.00 xxxx 1356 ATOM 1357 CD1 LEU A 176 61.175 12.071 95.308 1.00 0.00 xxxx 1357 ATOM 1358 CD2 LEU A 176 61.139 14.546 94.788 1.00 0.00 xxxx 1358 ATOM 1359 N GLN A 177 66.435 13.483 94.545 1.00 0.00 xxxx 1359 ATOM 1360 CA GLN A 177 67.817 13.462 95.029 1.00 0.00 xxxx 1360 ATOM 1361 C GLN A 177 68.693 12.943 93.896 1.00 0.00 xxxx 1361 ATOM 1362 O GLN A 177 68.228 12.150 93.071 1.00 0.00 xxxx 1362 ATOM 1363 CB GLN A 177 68.011 12.551 96.262 1.00 0.00 xxxx 1363 ATOM 1364 CG GLN A 177 66.981 12.631 97.393 1.00 0.00 xxxx 1364 ATOM 1365 CD GLN A 177 67.126 13.831 98.332 1.00 0.00 xxxx 1365 ATOM 1366 OE1 GLN A 177 66.270 14.034 99.194 1.00 0.00 xxxx 1366 ATOM 1367 NE2 GLN A 177 68.204 14.605 98.189 1.00 0.00 xxxx 1367 ATOM 1368 N LEU A 178 69.944 13.386 93.865 1.00 0.00 xxxx 1368 ATOM 1369 CA LEU A 178 70.942 12.869 92.930 1.00 0.00 xxxx 1369 ATOM 1370 C LEU A 178 72.319 13.073 93.530 1.00 0.00 xxxx 1370 ATOM 1371 O LEU A 178 72.658 14.177 93.954 1.00 0.00 xxxx 1371 ATOM 1372 CB LEU A 178 70.848 13.555 91.561 1.00 0.00 xxxx 1372 ATOM 1373 CG LEU A 178 71.737 12.993 90.440 1.00 0.00 xxxx 1373 ATOM 1374 CD1 LEU A 178 71.094 13.273 89.093 1.00 0.00 xxxx 1374 ATOM 1375 CD2 LEU A 178 73.146 13.573 90.458 1.00 0.00 xxxx 1375 ATOM 1376 N ASP A 179 73.110 12.011 93.565 1.00 0.00 xxxx 1376 ATOM 1377 CA ASP A 179 74.449 12.118 94.146 1.00 0.00 xxxx 1377 ATOM 1378 C ASP A 179 75.281 10.939 93.713 1.00 0.00 xxxx 1378 ATOM 1379 O ASP A 179 74.745 9.903 93.320 1.00 0.00 xxxx 1379 ATOM 1380 CB ASP A 179 74.373 12.174 95.674 1.00 0.00 xxxx 1380 ATOM 1381 CG ASP A 179 75.519 12.961 96.307 1.00 0.00 xxxx 1381 ATOM 1382 OD1 ASP A 179 76.586 13.168 95.674 1.00 0.00 xxxx 1382 ATOM 1383 OD2 ASP A 179 75.343 13.385 97.470 1.00 0.00 xxxx 1383 ATOM 1384 N THR A 180 76.599 11.086 93.801 1.00 0.00 xxxx 1384 ATOM 1385 CA THR A 180 77.473 9.975 93.475 1.00 0.00 xxxx 1385 ATOM 1386 C THR A 180 77.575 9.026 94.662 1.00 0.00 xxxx 1386 ATOM 1387 O THR A 180 77.531 9.442 95.826 1.00 0.00 xxxx 1387 ATOM 1388 CB THR A 180 78.880 10.457 93.069 1.00 0.00 xxxx 1388 ATOM 1389 OG1 THR A 180 79.674 9.327 92.674 1.00 0.00 xxxx 1389 ATOM 1390 CG2 THR A 180 79.568 11.183 94.230 1.00 0.00 xxxx 1390 ATOM 1391 N ALA A 181 77.682 7.739 94.364 1.00 0.00 xxxx 1391 ATOM 1392 CA ALA A 181 78.063 6.770 95.369 1.00 0.00 xxxx 1392 ATOM 1393 C ALA A 181 79.237 5.967 94.826 1.00 0.00 xxxx 1393 ATOM 1394 O ALA A 181 79.492 4.850 95.269 1.00 0.00 xxxx 1394 ATOM 1395 CB ALA A 181 76.890 5.868 95.738 1.00 0.00 xxxx 1395 ATOM 1396 N MET A 182 79.941 6.564 93.859 1.00 0.00 xxxx 1396 ATOM 1397 CA MET A 182 81.259 6.101 93.418 1.00 0.00 xxxx 1397 ATOM 1398 C MET A 182 81.306 4.625 93.052 1.00 0.00 xxxx 1398 ATOM 1399 O MET A 182 82.284 3.931 93.358 1.00 0.00 xxxx 1399 ATOM 1400 CB MET A 182 82.300 6.394 94.501 1.00 0.00 xxxx 1400 ATOM 1401 CG MET A 182 82.438 7.896 94.802 1.00 0.00 xxxx 1401 ATOM 1402 SD MET A 182 83.054 8.899 93.419 1.00 0.00 xxxx 1402 ATOM 1403 CE MET A 182 84.811 8.596 93.549 1.00 0.00 xxxx 1403 ATOM 1404 N CYS A 183 80.232 4.159 92.419 1.00 0.00 xxxx 1404 ATOM 1405 CA CYS A 183 80.152 2.815 91.855 1.00 0.00 xxxx 1405 ATOM 1406 C CYS A 183 80.215 1.715 92.915 1.00 0.00 xxxx 1406 ATOM 1407 O CYS A 183 80.418 0.555 92.578 1.00 0.00 xxxx 1407 ATOM 1408 CB CYS A 183 81.268 2.616 90.816 1.00 0.00 xxxx 1408 ATOM 1409 SG CYS A 183 81.332 4.000 89.637 1.00 0.00 xxxx 1409 ATOM 1410 N ASP A 184 79.976 2.079 94.179 1.00 0.00 xxxx 1410 ATOM 1411 CA ASP A 184 80.214 1.203 95.330 1.00 0.00 xxxx 1411 ATOM 1412 C ASP A 184 78.923 0.838 96.079 1.00 0.00 xxxx 1412 ATOM 1413 O ASP A 184 78.117 1.714 96.375 1.00 0.00 xxxx 1413 ATOM 1414 CB ASP A 184 81.210 1.895 96.281 1.00 0.00 xxxx 1414 ATOM 1415 CG ASP A 184 81.539 1.069 97.504 1.00 0.00 xxxx 1415 ATOM 1416 OD1 ASP A 184 82.395 0.168 97.414 1.00 0.00 xxxx 1416 ATOM 1417 OD2 ASP A 184 80.969 1.338 98.574 1.00 0.00 xxxx 1417 ATOM 1418 N THR A 185 78.740 −0.444 96.401 1.00 0.00 xxxx 1418 ATOM 1419 CA THR A 185 77.520 −0.913 97.077 1.00 0.00 xxxx 1419 ATOM 1420 C THR A 185 77.309 −0.291 98.464 1.00 0.00 xxxx 1420 ATOM 1421 O THR A 185 76.217 0.206 98.768 1.00 0.00 xxxx 1421 ATOM 1422 CB THR A 185 77.519 −2.460 97.230 1.00 0.00 xxxx 1422 ATOM 1423 OG1 THR A 185 77.522 −3.072 95.931 1.00 0.00 xxxx 1423 ATOM 1424 CG2 THR A 185 76.289 −2.934 97.982 1.00 0.00 xxxx 1424 ATOM 1425 N ALA A 186 78.331 −0.330 99.312 1.00 0.00 xxxx 1425 ATOM 1426 CA ALA A 186 78.187 0.212 100.664 1.00 0.00 xxxx 1426 ATOM 1427 C ALA A 186 77.948 1.725 100.657 1.00 0.00 xxxx 1427 ATOM 1428 O ALA A 186 77.117 2.229 101.429 1.00 0.00 xxxx 1428 ATOM 1429 CB ALA A 186 79.412 −0.129 101.507 1.00 0.00 xxxx 1429 ATOM 1430 N GLN A 187 78.647 2.454 99.792 1.00 0.00 xxxx 1430 ATOM 1431 CA GLN A 187 78.406 3.895 99.687 1.00 0.00 xxxx 1431 ATOM 1432 C GLN A 187 76.977 4.178 99.226 1.00 0.00 xxxx 1432 ATOM 1433 O GLN A 187 76.335 5.126 99.694 1.00 0.00 xxxx 1433 ATOM 1434 CB GLN A 187 79.390 4.562 98.725 1.00 0.00 xxxx 1434 ATOM 1435 CG GLN A 187 80.818 4.676 99.221 1.00 0.00 xxxx 1435 ATOM 1436 CD GLN A 187 81.613 5.683 98.408 1.00 0.00 xxxx 1436 ATOM 1437 OE1 GLN A 187 81.082 6.715 97.987 1.00 0.00 xxxx 1437 ATOM 1438 NE2 GLN A 187 82.885 5.385 98.173 1.00 0.00 xxxx 1438 ATOM 1439 N ALA A 188 76.470 3.356 98.313 1.00 0.00 xxxx 1439 ATOM 1440 CA ALA A 188 75.100 3.522 97.820 1.00 0.00 xxxx 1440 ATOM 1441 C ALA A 188 74.053 3.210 98.891 1.00 0.00 xxxx 1441 ATOM 1442 O ALA A 188 73.034 3.888 98.979 1.00 0.00 xxxx 1442 ATOM 1443 CB ALA A 188 74.877 2.642 96.604 1.00 0.00 xxxx 1443 ATOM 1444 N LYS A 189 74.302 2.173 99.690 1.00 0.00 xxxx 1444 ATOM 1445 CA LYS A 189 73.401 1.832 100.789 1.00 0.00 xxxx 1445 ATOM 1446 C LYS A 189 73.337 3.005 101.764 1.00 0.00 xxxx 1446 ATOM 1447 O LYS A 189 72.250 3.385 102.219 1.00 0.00 xxxx 1447 ATOM 1448 CB LYS A 189 73.860 0.551 101.506 1.00 0.00 xxxx 1448 ATOM 1449 CG LYS A 189 72.930 0.137 102.642 1.00 0.00 xxxx 1449 ATOM 1450 CD LYS A 189 73.420 −1.084 103.397 1.00 0.00 xxxx 1450 ATOM 1451 CE LYS A 189 72.458 −1.431 104.524 1.00 0.00 xxxx 1451 ATOM 1452 NZ LYS A 189 72.884 −2.636 105.292 1.00 0.00 xxxx 1452 ATOM 1453 N ASP A 190 74.502 3.586 102.066 1.00 0.00 xxxx 1453 ATOM 1454 CA ASP A 190 74.553 4.737 102.971 1.00 0.00 xxxx 1454 ATOM 1455 C ASP A 190 73.784 5.927 102.397 1.00 0.00 xxxx 1455 ATOM 1456 O ASP A 190 73.018 6.591 103.106 1.00 0.00 xxxx 1456 ATOM 1457 CB ASP A 190 75.996 5.149 103.260 1.00 0.00 xxxx 1457 ATOM 1458 CG ASP A 190 76.070 6.413 104.082 1.00 0.00 xxxx 1458 ATOM 1459 OD1 ASP A 190 75.855 6.332 105.307 1.00 0.00 xxxx 1459 ATOM 1460 OD2 ASP A 190 76.329 7.489 103.500 1.00 0.00 xxxx 1460 ATOM 1461 N LYS A 191 73.983 6.197 101.113 1.00 0.00 xxxx 1461 ATOM 1462 CA LYS A 191 73.330 7.344 100.479 1.00 0.00 xxxx 1462 ATOM 1463 C LYS A 191 71.811 7.147 100.415 1.00 0.00 xxxx 1463 ATOM 1464 O LYS A 191 71.035 8.050 100.762 1.00 0.00 xxxx 1464 ATOM 1465 CB LYS A 191 73.908 7.553 99.072 1.00 0.00 xxxx 1465 ATOM 1466 CG LYS A 191 73.374 8.747 98.322 1.00 0.00 xxxx 1466 ATOM 1467 CD LYS A 191 73.720 10.087 98.980 1.00 0.00 xxxx 1467 ATOM 1468 CE LYS A 191 75.228 10.258 99.200 1.00 0.00 xxxx 1468 ATOM 1469 NZ LYS A 191 75.550 11.651 99.690 1.00 0.00 xxxx 1469 ATOM 1470 N MET A 192 71.391 5.958 99.994 1.00 0.00 xxxx 1470 ATOM 1471 CA MET A 192 69.970 5.658 99.924 1.00 0.00 xxxx 1471 ATOM 1472 C MET A 192 69.313 5.698 101.304 1.00 0.00 xxxx 1472 ATOM 1473 O MET A 192 68.208 6.231 101.459 1.00 0.00 xxxx 1473 ATOM 1474 CB MET A 192 69.752 4.289 99.270 1.00 0.00 xxxx 1474 ATOM 1475 CG MET A 192 68.289 3.992 98.975 1.00 0.00 xxxx 1475 ATOM 1476 SD MET A 192 67.643 5.014 97.628 1.00 0.00 xxxx 1476 ATOM 1477 CE MET A 192 65.900 4.966 98.028 1.00 0.00 xxxx 1477 ATOM 1478 N ASP A 193 69.997 5.149 102.305 1.00 0.00 xxxx 1478 ATOM 1479 CA ASP A 193 69.495 5.202 103.671 1.00 0.00 xxxx 1479 ATOM 1480 C ASP A 193 69.318 6.653 104.133 1.00 0.00 xxxx 1480 ATOM 1481 O ASP A 193 68.323 6.989 104.793 1.00 0.00 xxxx 1481 ATOM 1482 CB ASP A 193 70.432 4.460 104.621 1.00 0.00 xxxx 1482 ATOM 1483 CG ASP A 193 69.987 4.572 106.057 1.00 0.00 xxxx 1483 ATOM 1484 OD1 ASP A 193 70.516 5.447 106.762 1.00 0.00 xxxx 1484 ATOM 1485 OD2 ASP A 193 69.077 3.814 106.469 1.00 0.00 xxxx 1485 ATOM 1486 N ALA A 194 70.274 7.516 103.797 1.00 0.00 xxxx 1486 ATOM 1487 CA ALA A 194 70.134 8.929 104.139 1.00 0.00 xxxx 1487 ATOM 1488 C ALA A 194 68.870 9.526 103.503 1.00 0.00 xxxx 1488 ATOM 1489 O ALA A 194 68.095 10.221 104.167 1.00 0.00 xxxx 1489 ATOM 1490 CB ALA A 194 71.377 9.712 103.703 1.00 0.00 xxxx 1490 ATOM 1491 N TRP A 195 68.656 9.239 102.224 1.00 0.00 xxxx 1491 ATOM 1492 CA TRP A 195 67.502 9.766 101.511 1.00 0.00 xxxx 1492 ATOM 1493 C TRP A 195 66.187 9.244 102.097 1.00 0.00 xxxx 1493 ATOM 1494 O TRP A 195 65.198 9.973 102.188 1.00 0.00 xxxx 1494 ATOM 1495 CB TRP A 195 67.624 9.412 100.034 1.00 0.00 xxxx 1495 ATOM 1496 CG TRP A 195 68.764 10.131 99.346 1.00 0.00 xxxx 1496 ATOM 1497 CD1 TRP A 195 69.427 11.225 99.801 1.00 0.00 xxxx 1497 ATOM 1498 CD2 TRP A 195 69.350 9.802 98.079 1.00 0.00 xxxx 1498 ATOM 1499 NE1 TRP A 195 70.403 11.602 98.894 1.00 0.00 xxxx 1499 ATOM 1500 CE2 TRP A 195 70.374 10.742 97.833 1.00 0.00 xxxx 1500 ATOM 1501 CE3 TRP A 195 69.116 8.799 97.135 1.00 0.00 xxxx 1501 ATOM 1502 CZ2 TRP A 195 71.149 10.719 96.668 1.00 0.00 xxxx 1502 ATOM 1503 CZ3 TRP A 195 69.898 8.779 95.971 1.00 0.00 xxxx 1503 ATOM 1504 CH2 TRP A 195 70.892 9.733 95.755 1.00 0.00 xxxx 1504 ATOM 1505 N LEU A 196 66.189 7.980 102.514 1.00 0.00 xxxx 1505 ATOM 1506 CA LEU A 196 65.022 7.406 103.164 1.00 0.00 xxxx 1506 ATOM 1507 C LEU A 196 64.808 7.957 104.566 1.00 0.00 xxxx 1507 ATOM 1508 O LEU A 196 63.775 7.692 105.177 1.00 0.00 xxxx 1508 ATOM 1509 CB LEU A 196 65.141 5.879 103.217 1.00 0.00 xxxx 1509 ATOM 1510 CG LEU A 196 65.043 5.236 101.832 1.00 0.00 xxxx 1510 ATOM 1511 CD1 LEU A 196 65.477 3.771 101.881 1.00 0.00 xxxx 1511 ATOM 1512 CD2 LEU A 196 63.614 5.360 101.304 1.00 0.00 xxxx 1512 ATOM 1513 N SER A 197 65.792 8.703 105.073 1.00 0.00 xxxx 1513 ATOM 1514 CA SER A 197 65.721 9.321 106.390 1.00 0.00 xxxx 1514 ATOM 1515 C SER A 197 65.516 10.830 106.277 1.00 0.00 xxxx 1515 ATOM 1516 O SER A 197 65.524 11.527 107.294 1.00 0.00 xxxx 1516 ATOM 1517 CB SER A 197 66.992 9.043 107.198 1.00 0.00 xxxx 1517 ATOM 1518 OG SER A 197 67.260 7.649 107.316 1.00 0.00 xxxx 1518 ATOM 1519 N GLY A 198 65.321 11.322 105.050 1.00 0.00 xxxx 1519 ATOM 1520 CA GLY A 198 65.148 12.751 104.807 1.00 0.00 xxxx 1520 ATOM 1521 C GLY A 198 63.742 13.078 104.341 1.00 0.00 xxxx 1521 ATOM 1522 O GLY A 198 62.900 12.186 104.216 1.00 0.00 xxxx 1522 ATOM 1523 N PRO A 199 63.478 14.363 104.074 1.00 0.00 xxxx 1523 ATOM 1524 CA PRO A 199 62.106 14.833 103.839 1.00 0.00 xxxx 1524 ATOM 1525 C PRO A 199 61.464 14.338 102.545 1.00 0.00 xxxx 1525 ATOM 1526 O PRO A 199 60.239 14.456 102.417 1.00 0.00 xxxx 1526 ATOM 1527 CB PRO A 199 62.254 16.364 103.800 1.00 0.00 xxxx 1527 ATOM 1528 CG PRO A 199 63.581 16.657 104.428 1.00 0.00 xxxx 1528 ATOM 1529 CD PRO A 199 64.450 15.464 104.162 1.00 0.00 xxxx 1529 ATOM 1530 N ASN A 200 62.245 13.815 101.604 1.00 0.00 xxxx 1530 ATOM 1531 CA ASN A 200 61.655 13.290 100.370 1.00 0.00 xxxx 1531 ATOM 1532 C ASN A 200 61.381 11.791 100.423 1.00 0.00 xxxx 1532 ATOM 1533 O ASN A 200 60.945 11.220 99.420 1.00 0.00 xxxx 1533 ATOM 1534 CB ASN A 200 62.557 13.582 99.166 1.00 0.00 xxxx 1534 ATOM 1535 CG ASN A 200 62.652 15.068 98.858 1.00 0.00 xxxx 1535 ATOM 1536 OD1 ASN A 200 61.657 15.795 98.911 1.00 0.00 xxxx 1536 ATOM 1537 ND2 ASN A 200 63.854 15.527 98.550 1.00 0.00 xxxx 1537 ATOM 1538 N ALA A 201 61.644 11.147 101.563 1.00 0.00 xxxx 1538 ATOM 1539 CA ALA A 201 61.533 9.689 101.645 1.00 0.00 xxxx 1539 ATOM 1540 C ALA A 201 60.185 9.168 101.122 1.00 0.00 xxxx 1540 ATOM 1541 O ALA A 201 60.157 8.216 100.329 1.00 0.00 xxxx 1541 ATOM 1542 CB ALA A 201 61.745 9.228 103.059 1.00 0.00 xxxx 1542 ATOM 1543 N ASN A 202 59.097 9.813 101.547 1.00 0.00 xxxx 1543 ATOM 1544 CA ASN A 202 57.746 9.334 101.237 1.00 0.00 xxxx 1544 ATOM 1545 C ASN A 202 57.364 9.580 99.785 1.00 0.00 xxxx 1545 ATOM 1546 O ASN A 202 56.394 8.997 99.291 1.00 0.00 xxxx 1546 ATOM 1547 CB ASN A 202 56.705 9.988 102.165 1.00 0.00 xxxx 1547 ATOM 1548 CG ASN A 202 56.603 11.501 101.979 1.00 0.00 xxxx 1548 ATOM 1549 OD1 ASN A 202 57.530 12.243 102.302 1.00 0.00 xxxx 1549 ATOM 1550 ND2 ASN A 202 55.465 11.961 101.474 1.00 0.00 xxxx 1550 ATOM 1551 N LYS A 203 58.134 10.428 99.110 1.00 0.00 xxxx 1551 ATOM 1552 CA LYS A 203 57.851 10.816 97.730 1.00 0.00 xxxx 1552 ATOM 1553 C LYS A 203 58.576 9.978 96.686 1.00 0.00 xxxx 1553 ATOM 1554 O LYS A 203 58.195 10.012 95.514 1.00 0.00 xxxx 1554 ATOM 1555 CB LYS A 203 58.218 12.287 97.509 1.00 0.00 xxxx 1555 ATOM 1556 CG LYS A 203 57.499 13.250 98.431 1.00 0.00 xxxx 1556 ATOM 1557 CD LYS A 203 57.973 14.674 98.189 1.00 0.00 xxxx 1557 ATOM 1558 CE LYS A 203 58.639 15.242 99.431 1.00 0.00 xxxx 1558 ATOM 1559 NZ LYS A 203 57.791 15.088 100.650 1.00 0.00 xxxx 1559 ATOM 1560 N ILE A 204 59.623 9.250 97.090 1.00 0.00 xxxx 1560 ATOM 1561 CA ILE A 204 60.423 8.457 96.146 1.00 0.00 xxxx 1561 ATOM 1562 C ILE A 204 59.602 7.349 95.500 1.00 0.00 xxxx 1562 ATOM 1563 O ILE A 204 59.039 6.510 96.207 1.00 0.00 xxxx 1563 ATOM 1564 CB ILE A 204 61.645 7.841 96.839 1.00 0.00 xxxx 1564 ATOM 1565 CG1 ILE A 204 62.522 8.943 97.425 1.00 0.00 xxxx 1565 ATOM 1566 CD1 ILE A 204 63.655 8.425 98.336 1.00 0.00 xxxx 1566 ATOM 1567 CG2 ILE A 204 62.435 6.991 95.839 1.00 0.00 xxxx 1567 ATOM 1568 N GLU A 205 59.555 7.333 94.165 1.00 0.00 xxxx 1568 ATOM 1569 CA GLU A 205 58.783 6.322 93.451 1.00 0.00 xxxx 1569 ATOM 1570 C GLU A 205 59.667 5.317 92.719 1.00 0.00 xxxx 1570 ATOM 1571 O GLU A 205 59.304 4.147 92.612 1.00 0.00 xxxx 1571 ATOM 1572 CB GLU A 205 57.816 6.995 92.459 1.00 0.00 xxxx 1572 ATOM 1573 CG GLU A 205 56.791 7.866 93.156 1.00 0.00 xxxx 1573 ATOM 1574 CD GLU A 205 55.895 8.673 92.223 1.00 0.00 xxxx 1574 ATOM 1575 OE1 GLU A 205 56.191 8.828 91.021 1.00 0.00 xxxx 1575 ATOM 1576 OE2 GLU A 205 54.874 9.172 92.719 1.00 0.00 xxxx 1576 ATOM 1577 N VAL A 206 60.811 5.774 92.213 1.00 0.00 xxxx 1577 ATOM 1578 CA VAL A 206 61.734 4.913 91.459 1.00 0.00 xxxx 1578 ATOM 1579 C VAL A 206 63.168 5.264 91.838 1.00 0.00 xxxx 1579 ATOM 1580 O VAL A 206 63.503 6.441 91.935 1.00 0.00 xxxx 1580 ATOM 1581 CB VAL A 206 61.525 5.069 89.927 1.00 0.00 xxxx 1581 ATOM 1582 CG1 VAL A 206 62.548 4.245 89.139 1.00 0.00 xxxx 1582 ATOM 1583 CG2 VAL A 206 60.096 4.661 89.499 1.00 0.00 xxxx 1583 ATOM 1584 N VAL A 207 64.011 4.250 92.037 1.00 0.00 xxxx 1584 ATOM 1585 CA VAL A 207 65.445 4.454 92.239 1.00 0.00 xxxx 1585 ATOM 1586 C VAL A 207 66.179 4.084 90.958 1.00 0.00 xxxx 1586 ATOM 1587 O VAL A 207 66.022 2.963 90.447 1.00 0.00 xxxx 1587 ATOM 1588 CB VAL A 207 65.991 3.618 93.404 1.00 0.00 xxxx 1588 ATOM 1589 CG1 VAL A 207 67.508 3.828 93.547 1.00 0.00 xxxx 1589 ATOM 1590 CG2 VAL A 207 65.272 3.946 94.703 1.00 0.00 xxxx 1590 ATOM 1591 N ILE A 208 66.982 5.022 90.448 1.00 0.00 xxxx 1591 ATOM 1592 CA ILE A 208 67.799 4.793 89.254 1.00 0.00 xxxx 1592 ATOM 1593 C ILE A 208 69.268 4.780 89.640 1.00 0.00 xxxx 1593 ATOM 1594 O ILE A 208 69.739 5.726 90.263 1.00 0.00 xxxx 1594 ATOM 1595 CB ILE A 208 67.549 5.872 88.194 1.00 0.00 xxxx 1595 ATOM 1596 CG1 ILE A 208 66.056 5.937 87.844 1.00 0.00 xxxx 1596 ATOM 1597 CD1 ILE A 208 65.698 7.103 86.935 1.00 0.00 xxxx 1597 ATOM 1598 CG2 ILE A 208 68.438 5.621 86.957 1.00 0.00 xxxx 1598 ATOM 1599 N ALA A 209 69.999 3.721 89.294 1.00 0.00 xxxx 1599 ATOM 1600 CA ALA A 209 71.437 3.691 89.582 1.00 0.00 xxxx 1600 ATOM 1601 C ALA A 209 72.264 3.519 88.307 1.00 0.00 xxxx 1601 ATOM 1602 O ALA A 209 71.869 2.778 87.405 1.00 0.00 xxxx 1602 ATOM 1603 CB ALA A 209 71.766 2.567 90.573 1.00 0.00 xxxx 1603 ATOM 1604 N ASN A 210 73.415 4.187 88.240 1.00 0.00 xxxx 1604 ATOM 1605 CA ASN A 210 74.296 4.064 87.076 1.00 0.00 xxxx 1605 ATOM 1606 C ASN A 210 74.921 2.682 86.965 1.00 0.00 xxxx 1606 ATOM 1607 O ASN A 210 75.438 2.334 85.907 1.00 0.00 xxxx 1607 ATOM 1608 CB ASN A 210 75.461 5.062 87.115 1.00 0.00 xxxx 1608 ATOM 1609 CG ASN A 210 75.095 6.511 86.761 1.00 0.00 xxxx 1609 ATOM 1610 OD1 ASN A 210 75.978 7.361 86.862 1.00 0.00 xxxx 1610 ATOM 1611 ND2 ASN A 210 73.853 6.799 86.348 1.00 0.00 xxxx 1611 ATOM 1612 N ASN A 211 74.967 1.918 88.058 1.00 0.00 xxxx 1612 ATOM 1613 CA ASN A 211 75.459 0.541 87.934 1.00 0.00 xxxx 1613 ATOM 1614 C ASN A 211 74.811 −0.377 88.967 1.00 0.00 xxxx 1614 ATOM 1615 O ASN A 211 74.096 0.077 89.878 1.00 0.00 xxxx 1615 ATOM 1616 CB ASN A 211 77.011 0.482 87.984 1.00 0.00 xxxx 1616 ATOM 1617 CG ASN A 211 77.609 0.592 89.395 1.00 0.00 xxxx 1617 ATOM 1618 OD1 ASN A 211 76.925 0.869 90.383 1.00 0.00 xxxx 1618 ATOM 1619 ND2 ASN A 211 78.929 0.407 89.473 1.00 0.00 xxxx 1619 ATOM 1620 N ASP A 212 75.007 −1.674 88.780 1.00 0.00 xxxx 1620 ATOM 1621 CA ASP A 212 74.353 −2.659 89.644 1.00 0.00 xxxx 1621 ATOM 1622 C ASP A 212 74.900 −2.644 91.056 1.00 0.00 xxxx 1622 ATOM 1623 O ASP A 212 74.155 −2.907 91.989 1.00 0.00 xxxx 1623 ATOM 1624 CB ASP A 212 74.504 −4.073 89.085 1.00 0.00 xxxx 1624 ATOM 1625 CG ASP A 212 73.580 −4.354 87.923 1.00 0.00 xxxx 1625 ATOM 1626 OD1 ASP A 212 72.644 −3.571 87.653 1.00 0.00 xxxx 1626 ATOM 1627 OD2 ASP A 212 73.801 −5.394 87.285 1.00 0.00 xxxx 1627 ATOM 1628 N ALA A 213 76.201 −2.392 91.216 1.00 0.00 xxxx 1628 ATOM 1629 CA ALA A 213 76.769 −2.347 92.563 1.00 0.00 xxxx 1629 ATOM 1630 C ALA A 213 75.986 −1.340 93.403 1.00 0.00 xxxx 1630 ATOM 1631 O ALA A 213 75.579 −1.630 94.539 1.00 0.00 xxxx 1631 ATOM 1632 CB ALA A 213 78.250 −1.988 92.519 1.00 0.00 xxxx 1632 ATOM 1633 N MET A 214 75.725 −0.174 92.827 1.00 0.00 xxxx 1633 ATOM 1634 CA MET A 214 74.991 0.841 93.567 1.00 0.00 xxxx 1634 ATOM 1635 C MET A 214 73.513 0.481 93.707 1.00 0.00 xxxx 1635 ATOM 1636 O MET A 214 72.916 0.724 94.758 1.00 0.00 xxxx 1636 ATOM 1637 CB MET A 214 75.173 2.215 92.911 1.00 0.00 xxxx 1637 ATOM 1638 CG MET A 214 76.604 2.734 93.068 1.00 0.00 xxxx 1638 ATOM 1639 SD MET A 214 76.846 4.394 92.423 1.00 0.00 xxxx 1639 ATOM 1640 CE MET A 214 76.387 4.154 90.695 1.00 0.00 xxxx 1640 ATOM 1641 N ALA A 215 72.917 −0.091 92.665 1.00 0.00 xxxx 1641 ATOM 1642 CA ALA A 215 71.533 −0.549 92.767 1.00 0.00 xxxx 1642 ATOM 1643 C ALA A 215 71.363 −1.525 93.930 1.00 0.00 xxxx 1643 ATOM 1644 O ALA A 215 70.377 −1.458 94.675 1.00 0.00 xxxx 1644 ATOM 1645 CB ALA A 215 71.087 −1.196 91.455 1.00 0.00 xxxx 1645 ATOM 1646 N MET A 216 72.321 −2.433 94.098 1.00 0.00 xxxx 1646 ATOM 1647 CA MET A 216 72.202 −3.437 95.149 1.00 0.00 xxxx 1647 ATOM 1648 C MET A 216 72.310 −2.813 96.539 1.00 0.00 xxxx 1648 ATOM 1649 O MET A 216 71.693 −3.301 97.484 1.00 0.00 xxxx 1649 ATOM 1650 CB MET A 216 73.251 −4.534 94.967 1.00 0.00 xxxx 1650 ATOM 1651 CG MET A 216 72.994 −5.385 93.737 1.00 0.00 xxxx 1651 ATOM 1652 SD MET A 216 74.066 −6.832 93.600 1.00 0.00 xxxx 1652 ATOM 1653 CE MET A 216 75.688 −6.071 93.652 1.00 0.00 xxxx 1653 ATOM 1654 N GLY A 217 73.077 −1.733 96.661 1.00 0.00 xxxx 1654 ATOM 1655 CA GLY A 217 73.106 −0.975 97.904 1.00 0.00 xxxx 1655 ATOM 1656 C GLY A 217 71.764 −0.328 98.196 1.00 0.00 xxxx 1656 ATOM 1657 O GLY A 217 71.289 −0.344 99.337 1.00 0.00 xxxx 1657 ATOM 1658 N ALA A 218 71.139 0.244 97.170 1.00 0.00 xxxx 1658 ATOM 1659 CA ALA A 218 69.812 0.848 97.344 1.00 0.00 xxxx 1659 ATOM 1660 C ALA A 218 68.782 −0.201 97.750 1.00 0.00 xxxx 1660 ATOM 1661 O ALA A 218 67.937 0.070 98.601 1.00 0.00 xxxx 1661 ATOM 1662 CB ALA A 218 69.368 1.554 96.064 1.00 0.00 xxxx 1662 ATOM 1663 N VAL A 219 68.859 −1.393 97.149 1.00 0.00 xxxx 1663 ATOM 1664 CA VAL A 219 67.943 −2.494 97.483 1.00 0.00 xxxx 1664 ATOM 1665 C VAL A 219 68.054 −2.817 98.970 1.00 0.00 xxxx 1665 ATOM 1666 O VAL A 219 67.038 −3.007 99.651 1.00 0.00 xxxx 1666 ATOM 1667 CB VAL A 219 68.231 −3.743 96.618 1.00 0.00 xxxx 1667 ATOM 1668 CG1 VAL A 219 67.526 −4.976 97.198 1.00 0.00 xxxx 1668 ATOM 1669 CG2 VAL A 219 67.771 −3.509 95.187 1.00 0.00 xxxx 1669 ATOM 1670 N GLU A 220 69.283 −2.856 99.481 1.00 0.00 xxxx 1670 ATOM 1671 CA GLU A 220 69.508 −3.155 100.894 1.00 0.00 xxxx 1671 ATOM 1672 C GLU A 220 68.901 −2.089 101.804 1.00 0.00 xxxx 1672 ATOM 1673 O GLU A 220 68.284 −2.411 102.827 1.00 0.00 xxxx 1673 ATOM 1674 CB GLU A 220 70.998 −3.275 101.196 1.00 0.00 xxxx 1674 ATOM 1675 CG GLU A 220 71.680 −4.536 100.690 1.00 0.00 xxxx 1675 ATOM 1676 CD GLU A 220 73.107 −4.637 101.220 1.00 0.00 xxxx 1676 ATOM 1677 OE1 GLU A 220 73.282 −4.770 102.453 1.00 0.00 xxxx 1677 ATOM 1678 OE2 GLU A 220 74.055 −4.552 100.413 1.00 0.00 xxxx 1678 ATOM 1679 N ALA A 221 69.094 −0.825 101.450 1.00 0.00 xxxx 1679 ATOM 1680 CA ALA A 221 68.532 0.265 102.247 1.00 0.00 xxxx 1680 ATOM 1681 C ALA A 221 67.006 0.221 102.244 1.00 0.00 xxxx 1681 ATOM 1682 O ALA A 221 66.362 0.410 103.284 1.00 0.00 xxxx 1682 ATOM 1683 CB ALA A 221 69.035 1.623 101.735 1.00 0.00 xxxx 1683 ATOM 1684 N LEU A 222 66.419 −0.050 101.085 1.00 0.00 xxxx 1684 ATOM 1685 CA LEU A 222 64.967 −0.103 100.981 1.00 0.00 xxxx 1685 ATOM 1686 C LEU A 222 64.414 −1.218 101.847 1.00 0.00 xxxx 1686 ATOM 1687 O LEU A 222 63.394 −1.040 102.523 1.00 0.00 xxxx 1687 ATOM 1688 CB LEU A 222 64.534 −0.285 99.521 1.00 0.00 xxxx 1688 ATOM 1689 CG LEU A 222 64.657 0.972 98.647 1.00 0.00 xxxx 1689 ATOM 1690 CD1 LEU A 222 64.575 0.602 97.175 1.00 0.00 xxxx 1690 ATOM 1691 CD2 LEU A 222 63.573 1.992 98.994 1.00 0.00 xxxx 1691 ATOM 1692 N LYS A 223 65.098 −2.360 101.853 1.00 0.00 xxxx 1692 ATOM 1693 CA LYS A 223 64.672 −3.492 102.687 1.00 0.00 xxxx 1693 ATOM 1694 C LYS A 223 64.691 −3.123 104.174 1.00 0.00 xxxx 1694 ATOM 1695 O LYS A 223 63.776 −3.473 104.932 1.00 0.00 xxxx 1695 ATOM 1696 CB LYS A 223 65.558 −4.718 102.435 1.00 0.00 xxxx 1696 ATOM 1697 CG LYS A 223 65.379 −5.837 103.462 1.00 0.00 xxxx 1697 ATOM 1698 CD LYS A 223 66.047 −7.129 103.009 1.00 0.00 xxxx 1698 ATOM 1699 CE LYS A 223 67.535 −6.935 102.773 1.00 0.00 xxxx 1699 ATOM 1700 NZ LYS A 223 68.181 −8.167 102.241 1.00 0.00 xxxx 1700 ATOM 1701 N ALA A 224 65.724 −2.401 104.585 1.00 0.00 xxxx 1701 ATOM 1702 CA ALA A 224 65.845 −1.978 105.975 1.00 0.00 xxxx 1702 ATOM 1703 C ALA A 224 64.728 −1.013 106.394 1.00 0.00 xxxx 1703 ATOM 1704 O ALA A 224 64.380 −0.950 107.574 1.00 0.00 xxxx 1704 ATOM 1705 CB ALA A 224 67.209 −1.344 106.206 1.00 0.00 xxxx 1705 ATOM 1706 N HIS A 225 64.162 −0.281 105.437 1.00 0.00 xxxx 1706 ATOM 1707 CA HIS A 225 63.105 0.692 105.703 1.00 0.00 xxxx 1707 ATOM 1708 C HIS A 225 61.712 0.158 105.372 1.00 0.00 xxxx 1708 ATOM 1709 O HIS A 225 60.742 0.921 105.364 1.00 0.00 xxxx 1709 ATOM 1710 CB HIS A 225 63.340 1.974 104.904 1.00 0.00 xxxx 1710 ATOM 1711 CG HIS A 225 64.419 2.844 105.462 1.00 0.00 xxxx 1711 ATOM 1712 ND1 HIS A 225 64.152 3.941 106.253 1.00 0.00 xxxx 1712 ATOM 1713 CD2 HIS A 225 65.767 2.774 105.352 1.00 0.00 xxxx 1713 ATOM 1714 CE1 HIS A 225 65.292 4.512 106.605 1.00 0.00 xxxx 1714 ATOM 1715 NE2 HIS A 225 66.287 3.823 106.074 1.00 0.00 xxxx 1715 ATOM 1716 N ASN A 226 61.631 −1.139 105.081 1.00 0.00 xxxx 1716 ATOM 1717 CA ASN A 226 60.369 −1.793 104.741 1.00 0.00 xxxx 1717 ATOM 1718 C ASN A 226 59.709 −1.111 103.554 1.00 0.00 xxxx 1718 ATOM 1719 O ASN A 226 58.492 −0.887 103.539 1.00 0.00 xxxx 1719 ATOM 1720 CB ASN A 226 59.430 −1.807 105.947 1.00 0.00 xxxx 1720 ATOM 1721 CG ASN A 226 60.045 −2.499 107.142 1.00 0.00 xxxx 1721 ATOM 1722 OD1 ASN A 226 60.652 −3.561 107.007 1.00 0.00 xxxx 1722 ATOM 1723 ND2 ASN A 226 59.909 −1.893 108.317 1.00 0.00 xxxx 1723 ATOM 1724 N LYS A 227 60.537 −0.777 102.565 1.00 0.00 xxxx 1724 ATOM 1725 CA LYS A 227 60.095 −0.116 101.349 1.00 0.00 xxxx 1725 ATOM 1726 C LYS A 227 60.554 −0.907 100.120 1.00 0.00 xxxx 1726 ATOM 1727 O LYS A 227 60.903 −0.320 99.095 1.00 0.00 xxxx 1727 ATOM 1728 CB LYS A 227 60.642 1.319 101.285 1.00 0.00 xxxx 1728 ATOM 1729 CG LYS A 227 60.066 2.283 102.323 1.00 0.00 xxxx 1729 ATOM 1730 CD LYS A 227 58.656 2.733 101.966 1.00 0.00 xxxx 1730 ATOM 1731 CE LYS A 227 58.656 3.636 100.738 1.00 0.00 xxxx 1731 ATOM 1732 NZ LYS A 227 57.319 4.258 100.483 1.00 0.00 xxxx 1732 ATOM 1733 N SER A 228 60.548 −2.232 100.216 1.00 0.00 xxxx 1733 ATOM 1734 CA SER A 228 61.005 −3.057 99.100 1.00 0.00 xxxx 1734 ATOM 1735 C SER A 228 60.051 −3.004 97.906 1.00 0.00 xxxx 1735 ATOM 1736 O SER A 228 60.369 −3.529 96.837 1.00 0.00 xxxx 1736 ATOM 1737 CB SER A 228 61.196 −4.502 99.550 1.00 0.00 xxxx 1737 ATOM 1738 OG SER A 228 62.308 −4.609 100.420 1.00 0.00 xxxx 1738 ATOM 1739 N SER A 229 58.902 −2.360 98.089 1.00 0.00 xxxx 1739 ATOM 1740 CA SER A 229 57.932 −2.158 97.014 1.00 0.00 xxxx 1740 ATOM 1741 C SER A 229 58.391 −1.094 96.013 1.00 0.00 xxxx 1741 ATOM 1742 O SER A 229 57.823 −0.972 94.930 1.00 0.00 xxxx 1742 ATOM 1743 CB SER A 229 56.570 −1.768 97.604 1.00 0.00 xxxx 1743 ATOM 1744 OG SER A 229 56.710 −0.696 98.528 1.00 0.00 xxxx 1744 ATOM 1745 N ILE A 230 59.404 −0.317 96.393 1.00 0.00 xxxx 1745 ATOM 1746 CA ILE A 230 59.980 0.706 95.516 1.00 0.00 xxxx 1746 ATOM 1747 C ILE A 230 60.940 0.056 94.525 1.00 0.00 xxxx 1747 ATOM 1748 O ILE A 230 61.918 −0.553 94.936 1.00 0.00 xxxx 1748 ATOM 1749 CB ILE A 230 60.719 1.781 96.334 1.00 0.00 xxxx 1749 ATOM 1750 CG2 ILE A 230 61.325 2.840 95.416 1.00 0.00 xxxx 1750 ATOM 1751 CG1 ILE A 230 59.795 2.397 97.395 1.00 0.00 xxxx 1751 ATOM 1752 CD1 ILE A 230 58.589 3.105 96.823 1.00 0.00 xxxx 1752 ATOM 1753 N PRO A 231 60.674 0.191 93.219 1.00 0.00 xxxx 1753 ATOM 1754 CA PRO A 231 61.546 −0.457 92.223 1.00 0.00 xxxx 1754 ATOM 1755 C PRO A 231 62.907 0.219 92.060 1.00 0.00 xxxx 1755 ATOM 1756 O PRO A 231 63.019 1.446 92.161 1.00 0.00 xxxx 1756 ATOM 1757 CB PRO A 231 60.746 −0.329 90.932 1.00 0.00 xxxx 1757 ATOM 1758 CG PRO A 231 59.952 0.924 91.123 1.00 0.00 xxxx 1758 ATOM 1759 CD PRO A 231 59.570 0.934 92.587 1.00 0.00 xxxx 1759 ATOM 1760 N VAL A 232 63.918 −0.603 91.789 1.00 0.00 xxxx 1760 ATOM 1761 CA VAL A 232 65.289 −0.161 91.571 1.00 0.00 xxxx 1761 ATOM 1762 C VAL A 232 65.746 −0.630 90.193 1.00 0.00 xxxx 1762 ATOM 1763 O VAL A 232 65.467 −1.756 89.787 1.00 0.00 xxxx 1763 ATOM 1764 CB VAL A 232 66.224 −0.701 92.662 1.00 0.00 xxxx 1764 ATOM 1765 CG1 VAL A 232 67.645 −0.189 92.454 1.00 0.00 xxxx 1765 ATOM 1766 CG2 VAL A 232 65.710 −0.305 94.046 1.00 0.00 xxxx 1766 ATOM 1767 N PHE A 233 66.444 0.246 89.479 1.00 0.00 xxxx 1767 ATOM 1768 CA PHE A 233 67.018 −0.105 88.177 1.00 0.00 xxxx 1768 ATOM 1769 C PHE A 233 68.529 0.093 88.187 1.00 0.00 xxxx 1769 ATOM 1770 O PHE A 233 69.029 1.058 88.763 1.00 0.00 xxxx 1770 ATOM 1771 CB PHE A 233 66.384 0.735 87.069 1.00 0.00 xxxx 1771 ATOM 1772 CG PHE A 233 64.923 0.445 86.854 1.00 0.00 xxxx 1772 ATOM 1773 CD1 PHE A 233 64.525 −0.446 85.872 1.00 0.00 xxxx 1773 ATOM 1774 CD2 PHE A 233 63.955 1.050 87.647 1.00 0.00 xxxx 1774 ATOM 1775 CE1 PHE A 233 63.175 −0.719 85.664 1.00 0.00 xxxx 1775 ATOM 1776 CE2 PHE A 233 62.612 0.777 87.459 1.00 0.00 xxxx 1776 ATOM 1777 CZ PHE A 233 62.217 −0.110 86.470 1.00 0.00 xxxx 1777 ATOM 1778 N GLY A 234 69.252 −0.834 87.556 1.00 0.00 xxxx 1778 ATOM 1779 CA GLY A 234 70.704 −0.748 87.481 1.00 0.00 xxxx 1779 ATOM 1780 C GLY A 234 71.251 −0.871 86.071 1.00 0.00 xxxx 1780 ATOM 1781 O GLY A 234 70.506 −0.818 85.087 1.00 0.00 xxxx 1781 ATOM 1782 N VAL A 235 72.572 −1.000 85.997 1.00 0.00 xxxx 1782 ATOM 1783 CA VAL A 235 73.304 −1.326 84.767 1.00 0.00 xxxx 1783 ATOM 1784 C VAL A 235 74.447 −2.269 85.103 1.00 0.00 xxxx 1784 ATOM 1785 O VAL A 235 75.187 −2.003 86.057 1.00 0.00 xxxx 1785 ATOM 1786 CB VAL A 235 73.881 −0.073 84.066 1.00 0.00 xxxx 1786 ATOM 1787 CG1 VAL A 235 74.730 −0.490 82.870 1.00 0.00 xxxx 1787 ATOM 1788 CG2 VAL A 235 72.785 0.883 83.642 1.00 0.00 xxxx 1788 ATOM 1789 N ASP A 236 74.550 −3.356 84.329 1.00 0.00 xxxx 1789 ATOM 1790 CA ASP A 236 75.711 −4.274 84.192 1.00 0.00 xxxx 1790 ATOM 1791 C ASP A 236 75.229 −5.706 83.994 1.00 0.00 xxxx 1791 ATOM 1792 O ASP A 236 75.867 −6.481 83.286 1.00 0.00 xxxx 1792 ATOM 1793 CB ASP A 236 76.688 −4.255 85.385 1.00 0.00 xxxx 1793 ATOM 1794 CG ASP A 236 77.665 −3.089 85.333 1.00 0.00 xxxx 1794 ATOM 1795 OD1 ASP A 236 77.845 −2.486 84.251 1.00 0.00 xxxx 1795 ATOM 1796 OD2 ASP A 236 78.254 −2.760 86.388 1.00 0.00 xxxx 1796 ATOM 1797 N ALA A 237 74.107 −6.042 84.628 1.00 0.00 xxxx 1797 ATOM 1798 CA ALA A 237 73.631 −7.418 84.752 1.00 0.00 xxxx 1798 ATOM 1799 C ALA A 237 74.721 −8.308 85.339 1.00 0.00 xxxx 1799 ATOM 1800 O ALA A 237 75.071 −9.350 84.775 1.00 0.00 xxxx 1800 ATOM 1801 CB ALA A 237 73.144 −7.963 83.398 1.00 0.00 xxxx 1801 ATOM 1802 N LEU A 238 75.253 −7.893 86.487 1.00 0.00 xxxx 1802 ATOM 1803 CA LEU A 238 76.190 −8.722 87.231 1.00 0.00 xxxx 1803 ATOM 1804 C LEU A 238 75.508 −10.035 87.568 1.00 0.00 xxxx 1804 ATOM 1805 O LEU A 238 74.304 −10.059 87.782 1.00 0.00 xxxx 1805 ATOM 1806 CB LEU A 238 76.642 −8.041 88.525 1.00 0.00 xxxx 1806 ATOM 1807 CG LEU A 238 77.270 −6.648 88.486 1.00 0.00 xxxx 1807 ATOM 1808 CD1 LEU A 238 77.388 −6.142 89.909 1.00 0.00 xxxx 1808 ATOM 1809 CD2 LEU A 238 78.643 −6.698 87.820 1.00 0.00 xxxx 1809 ATOM 1810 N PRO A 239 76.280 −11.130 87.626 1.00 0.00 xxxx 1810 ATOM 1811 CA PRO A 239 75.700 −12.410 88.037 1.00 0.00 xxxx 1811 ATOM 1812 C PRO A 239 74.853 −12.285 89.303 1.00 0.00 xxxx 1812 ATOM 1813 O PRO A 239 73.767 −12.852 89.361 1.00 0.00 xxxx 1813 ATOM 1814 CB PRO A 239 76.932 −13.286 88.276 1.00 0.00 xxxx 1814 ATOM 1815 CG PRO A 239 77.965 −12.728 87.363 1.00 0.00 xxxx 1815 ATOM 1816 CD PRO A 239 77.718 −11.238 87.325 1.00 0.00 xxxx 1816 ATOM 1817 N GLU A 240 75.322 −11.516 90.284 1.00 0.00 xxxx 1817 ATOM 1818 CA GLU A 240 74.596 −11.373 91.544 1.00 0.00 xxxx 1818 ATOM 1819 C GLU A 240 73.346 −10.497 91.399 1.00 0.00 xxxx 1819 ATOM 1820 O GLU A 240 72.385 −10.645 92.152 1.00 0.00 xxxx 1820 ATOM 1821 CB GLU A 240 75.518 −10.812 92.638 1.00 0.00 xxxx 1821 ATOM 1822 CG GLU A 240 76.280 −9.539 92.268 1.00 0.00 xxxx 1822 ATOM 1823 CD GLU A 240 77.688 −9.807 91.744 1.00 0.00 xxxx 1823 ATOM 1824 OE1 GLU A 240 77.872 −10.780 90.977 1.00 0.00 xxxx 1824 ATOM 1825 OE2 GLU A 240 78.614 −9.041 92.101 1.00 0.00 xxxx 1825 ATOM 1826 N ALA A 241 73.349 −9.599 90.421 1.00 0.00 xxxx 1826 ATOM 1827 CA ALA A 241 72.181 −8.751 90.182 1.00 0.00 xxxx 1827 ATOM 1828 C ALA A 241 71.053 −9.528 89.496 1.00 0.00 xxxx 1828 ATOM 1829 O ALA A 241 69.870 −9.257 89.712 1.00 0.00 xxxx 1829 ATOM 1830 CB ALA A 241 72.572 −7.540 89.350 1.00 0.00 xxxx 1830 ATOM 1831 N LEU A 242 71.423 −10.495 88.663 1.00 0.00 xxxx 1831 ATOM 1832 CA LEU A 242 70.431 −11.298 87.963 1.00 0.00 xxxx 1832 ATOM 1833 C LEU A 242 69.530 −12.038 88.950 1.00 0.00 xxxx 1833 ATOM 1834 O LEU A 242 68.339 −12.213 88.703 1.00 0.00 xxxx 1834 ATOM 1835 CB LEU A 242 71.118 −12.279 87.010 1.00 0.00 xxxx 1835 ATOM 1836 CG LEU A 242 71.898 −11.594 85.884 1.00 0.00 xxxx 1836 ATOM 1837 CD1 LEU A 242 72.501 −12.613 84.916 1.00 0.00 xxxx 1837 ATOM 1838 CD2 LEU A 242 71.012 −10.605 85.142 1.00 0.00 xxxx 1838 ATOM 1839 N ALA A 243 70.095 −12.448 90.081 1.00 0.00 xxxx 1839 ATOM 1840 CA ALA A 243 69.326 −13.136 91.107 1.00 0.00 xxxx 1840 ATOM 1841 C ALA A 243 68.253 −12.225 91.705 1.00 0.00 xxxx 1841 ATOM 1842 O ALA A 243 67.158 −12.675 92.032 1.00 0.00 xxxx 1842 ATOM 1843 CB ALA A 243 70.249 −13.654 92.196 1.00 0.00 xxxx 1843 ATOM 1844 N LEU A 244 68.574 −10.940 91.839 1.00 0.00 xxxx 1844 ATOM 1845 CA LEU A 244 67.627 −9.962 92.351 1.00 0.00 xxxx 1845 ATOM 1846 C LEU A 244 66.537 −9.636 91.338 1.00 0.00 xxxx 1846 ATOM 1847 O LEU A 244 65.422 −9.284 91.715 1.00 0.00 xxxx 1847 ATOM 1848 CB LEU A 244 68.346 −8.675 92.751 1.00 0.00 xxxx 1848 ATOM 1849 CG LEU A 244 69.396 −8.786 93.856 1.00 0.00 xxxx 1849 ATOM 1850 CD1 LEU A 244 70.017 −7.425 94.111 1.00 0.00 xxxx 1850 ATOM 1851 CD2 LEU A 244 68.793 −9.348 95.137 1.00 0.00 xxxx 1851 ATOM 1852 N VAL A 245 66.867 −9.713 90.050 1.00 0.00 xxxx 1852 ATOM 1853 CA VAL A 245 65.847 −9.540 89.027 1.00 0.00 xxxx 1853 ATOM 1854 C VAL A 245 64.835 −10.677 89.141 1.00 0.00 xxxx 1854 ATOM 1855 O VAL A 245 63.629 −10.467 89.025 1.00 0.00 xxxx 1855 ATOM 1856 CB VAL A 245 66.460 −9.483 87.612 1.00 0.00 xxxx 1856 ATOM 1857 CG1 VAL A 245 65.348 −9.436 86.568 1.00 0.00 xxxx 1857 ATOM 1858 CG2 VAL A 245 67.385 −8.263 87.487 1.00 0.00 xxxx 1858 ATOM 1859 N LYS A 246 65.342 −11.882 89.377 1.00 0.00 xxxx 1859 ATOM 1860 CA LYS A 246 64.486 −13.053 89.565 1.00 0.00 xxxx 1860 ATOM 1861 C LYS A 246 63.547 −12.843 90.752 1.00 0.00 xxxx 1861 ATOM 1862 O LYS A 246 62.342 −13.073 90.651 1.00 0.00 xxxx 1862 ATOM 1863 CB LYS A 246 65.339 −14.313 89.764 1.00 0.00 xxxx 1863 ATOM 1864 CG LYS A 246 64.560 −15.639 89.744 1.00 0.00 xxxx 1864 ATOM 1865 CD LYS A 246 64.000 −16.017 91.119 1.00 0.00 xxxx 1865 ATOM 1866 CE LYS A 246 62.993 −17.166 91.028 1.00 0.00 xxxx 1866 ATOM 1867 NZ LYS A 246 62.123 −17.249 92.240 1.00 0.00 xxxx 1867 ATOM 1868 N SER A 247 64.105 −12.396 91.874 1.00 0.00 xxxx 1868 ATOM 1869 CA SER A 247 63.342 −12.267 93.110 1.00 0.00 xxxx 1869 ATOM 1870 C SER A 247 62.398 −11.073 93.075 1.00 0.00 xxxx 1870 ATOM 1871 O SER A 247 61.460 −10.990 93.870 1.00 0.00 xxxx 1871 ATOM 1872 CB SER A 247 64.286 −12.144 94.308 1.00 0.00 xxxx 1872 ATOM 1873 OG SER A 247 64.953 −10.894 94.307 1.00 0.00 xxxx 1873 ATOM 1874 N GLY A 248 62.647 −10.151 92.152 1.00 0.00 xxxx 1874 ATOM 1875 CA GLY A 248 61.848 −8.948 92.052 1.00 0.00 xxxx 1875 ATOM 1876 C GLY A 248 62.402 −7.796 92.873 1.00 0.00 xxxx 1876 ATOM 1877 O GLY A 248 61.832 −6.709 92.881 1.00 0.00 xxxx 1877 ATOM 1878 N ALA A 249 63.517 −8.035 93.561 1.00 0.00 xxxx 1878 ATOM 1879 CA ALA A 249 64.176 −6.992 94.350 1.00 0.00 xxxx 1879 ATOM 1880 C ALA A 249 64.775 −5.920 93.447 1.00 0.00 xxxx 1880 ATOM 1881 O ALA A 249 64.873 −4.756 93.827 1.00 0.00 xxxx 1881 ATOM 1882 CB ALA A 249 65.253 −7.598 95.238 1.00 0.00 xxxx 1882 ATOM 1883 N LEU A 250 65.185 −6.328 92.249 1.00 0.00 xxxx 1883 ATOM 1884 CA LEU A 250 65.663 −5.410 91.230 1.00 0.00 xxxx 1884 ATOM 1885 C LEU A 250 64.692 −5.468 90.058 1.00 0.00 xxxx 1885 ATOM 1886 O LEU A 250 64.411 −6.547 89.548 1.00 0.00 xxxx 1886 ATOM 1887 CB LEU A 250 67.085 −5.785 90.790 1.00 0.00 xxxx 1887 ATOM 1888 CG LEU A 250 67.898 −4.821 89.938 1.00 0.00 xxxx 1888 ATOM 1889 CD1 LEU A 250 68.214 −3.556 90.736 1.00 0.00 xxxx 1889 ATOM 1890 CD2 LEU A 250 69.171 −5.513 89.483 1.00 0.00 xxxx 1890 ATOM 1891 N ALA A 251 64.174 −4.319 89.633 1.00 0.00 xxxx 1891 ATOM 1892 CA ALA A 251 63.132 −4.291 88.613 1.00 0.00 xxxx 1892 ATOM 1893 C ALA A 251 63.704 −4.469 87.215 1.00 0.00 xxxx 1893 ATOM 1894 O ALA A 251 63.030 −4.971 86.310 1.00 0.00 xxxx 1894 ATOM 1895 CB ALA A 251 62.332 −2.985 88.696 1.00 0.00 xxxx 1895 ATOM 1896 N GLY A 252 64.944 −4.045 87.024 1.00 0.00 xxxx 1896 ATOM 1897 CA GLY A 252 65.556 −4.215 85.724 1.00 0.00 xxxx 1897 ATOM 1898 C GLY A 252 66.982 −3.738 85.694 1.00 0.00 xxxx 1898 ATOM 1899 O GLY A 252 67.396 −2.934 86.528 1.00 0.00 xxxx 1899 ATOM 1900 N THR A 253 67.743 −4.243 84.733 1.00 0.00 xxxx 1900 ATOM 1901 CA THR A 253 69.114 −3.796 84.577 1.00 0.00 xxxx 1901 ATOM 1902 C THR A 253 69.496 −3.891 83.101 1.00 0.00 xxxx 1902 ATOM 1903 O THR A 253 68.648 −4.124 82.251 1.00 0.00 xxxx 1903 ATOM 1904 CB THR A 253 70.078 −4.617 85.488 1.00 0.00 xxxx 1904 ATOM 1905 OG1 THR A 253 71.414 −4.114 85.371 1.00 0.00 xxxx 1905 ATOM 1906 CG2 THR A 253 70.046 −6.088 85.134 1.00 0.00 xxxx 1906 ATOM 1907 N VAL A 254 70.761 −3.655 82.788 1.00 0.00 xxxx 1907 ATOM 1908 CA VAL A 254 71.210 −3.611 81.398 1.00 0.00 xxxx 1908 ATOM 1909 C VAL A 254 72.503 −4.399 81.301 1.00 0.00 xxxx 1909 ATOM 1910 O VAL A 254 73.468 −4.053 81.986 1.00 0.00 xxxx 1910 ATOM 1911 CB VAL A 254 71.438 −2.156 80.931 1.00 0.00 xxxx 1911 ATOM 1912 CG1 VAL A 254 71.966 −2.120 79.492 1.00 0.00 xxxx 1912 ATOM 1913 CG2 VAL A 254 70.181 −1.298 81.103 1.00 0.00 xxxx 1913 ATOM 1914 N LEU A 255 72.552 −5.426 80.454 1.00 0.00 xxxx 1914 ATOM 1915 CA LEU A 255 73.785 −6.208 80.315 1.00 0.00 xxxx 1915 ATOM 1916 C LEU A 255 74.913 −5.348 79.768 1.00 0.00 xxxx 1916 ATOM 1917 O LEU A 255 74.817 −4.771 78.689 1.00 0.00 xxxx 1917 ATOM 1918 CB LEU A 255 73.580 −7.439 79.413 1.00 0.00 xxxx 1918 ATOM 1919 CG LEU A 255 74.896 −8.169 79.088 1.00 0.00 xxxx 1919 ATOM 1920 CD1 LEU A 255 75.517 −8.756 80.351 1.00 0.00 xxxx 1920 ATOM 1921 CD2 LEU A 255 74.714 −9.252 78.028 1.00 0.00 xxxx 1921 ATOM 1922 N ASN A 256 75.962 −5.224 80.567 1.00 0.00 xxxx 1922 ATOM 1923 CA ASN A 256 77.230 −4.676 80.127 1.00 0.00 xxxx 1923 ATOM 1924 C ASN A 256 78.070 −5.920 79.866 1.00 0.00 xxxx 1924 ATOM 1925 O ASN A 256 78.364 −6.686 80.785 1.00 0.00 xxxx 1925 ATOM 1926 CB ASN A 256 77.809 −3.752 81.206 1.00 0.00 xxxx 1926 ATOM 1927 CG ASN A 256 79.029 −2.990 80.750 1.00 0.00 xxxx 1927 ATOM 1928 OD1 ASN A 256 79.481 −3.121 79.606 1.00 0.00 xxxx 1928 ATOM 1929 ND2 ASN A 256 79.565 −2.163 81.641 1.00 0.00 xxxx 1929 ATOM 1930 N ASP A 257 78.380 −6.168 78.598 1.00 0.00 xxxx 1930 ATOM 1931 CA ASP A 257 78.822 −7.494 78.170 1.00 0.00 xxxx 1931 ATOM 1932 C ASP A 257 80.300 −7.722 78.470 1.00 0.00 xxxx 1932 ATOM 1933 O ASP A 257 81.161 −7.511 77.613 1.00 0.00 xxxx 1933 ATOM 1934 CB ASP A 257 78.534 −7.665 76.672 1.00 0.00 xxxx 1934 ATOM 1935 CG ASP A 257 78.715 −9.097 76.179 1.00 0.00 xxxx 1935 ATOM 1936 OD1 ASP A 257 79.319 −9.930 76.887 1.00 0.00 xxxx 1936 ATOM 1937 OD2 ASP A 257 78.240 −9.391 75.055 1.00 0.00 xxxx 1937 ATOM 1938 N ALA A 258 80.572 −8.161 79.697 1.00 0.00 xxxx 1938 ATOM 1939 CA ALA A 258 81.936 −8.390 80.176 1.00 0.00 xxxx 1939 ATOM 1940 C ALA A 258 82.663 −9.456 79.370 1.00 0.00 xxxx 1940 ATOM 1941 O ALA A 258 83.844 −9.286 79.049 1.00 0.00 xxxx 1941 ATOM 1942 CB ALA A 258 81.915 −8.787 81.645 1.00 0.00 xxxx 1942 ATOM 1943 N ASN A 259 81.969 −10.547 79.044 1.00 0.00 xxxx 1943 ATOM 1944 CA ASN A 259 82.608 −11.662 78.360 1.00 0.00 xxxx 1944 ATOM 1945 C ASN A 259 83.116 −11.236 76.988 1.00 0.00 xxxx 1945 ATOM 1946 O ASN A 259 84.233 −11.586 76.606 1.00 0.00 xxxx 1946 ATOM 1947 CB ASN A 259 81.649 −12.850 78.230 1.00 0.00 xxxx 1947 ATOM 1948 CG ASN A 259 81.281 −13.441 79.572 1.00 0.00 xxxx 1948 ATOM 1949 OD1 ASN A 259 82.086 −13.437 80.505 1.00 0.00 xxxx 1949 ATOM 1950 ND2 ASN A 259 80.055 −13.946 79.683 1.00 0.00 xxxx 1950 ATOM 1951 N ASN A 260 82.323 −10.460 76.251 1.00 0.00 xxxx 1951 ATOM 1952 CA ASN A 260 82.768 −10.060 74.925 1.00 0.00 xxxx 1952 ATOM 1953 C ASN A 260 83.762 −8.902 74.974 1.00 0.00 xxxx 1953 ATOM 1954 O ASN A 260 84.652 −8.842 74.128 1.00 0.00 xxxx 1954 ATOM 1955 CB ASN A 260 81.570 −9.722 74.037 1.00 0.00 xxxx 1955 ATOM 1956 CG ASN A 260 80.950 −10.969 73.440 1.00 0.00 xxxx 1956 ATOM 1957 OD1 ASN A 260 81.669 −11.860 72.978 1.00 0.00 xxxx 1957 ATOM 1958 ND2 ASN A 260 79.627 −11.059 73.469 1.00 0.00 xxxx 1958 ATOM 1959 N GLN A 261 83.665 −8.012 75.961 1.00 0.00 xxxx 1959 ATOM 1960 CA GLN A 261 84.693 −6.975 76.100 1.00 0.00 xxxx 1960 ATOM 1961 C GLN A 261 86.041 −7.609 76.481 1.00 0.00 xxxx 1961 ATOM 1962 O GLN A 261 87.080 −7.215 75.948 1.00 0.00 xxxx 1962 ATOM 1963 CB GLN A 261 84.267 −5.916 77.107 1.00 0.00 xxxx 1963 ATOM 1964 CG GLN A 261 83.183 −5.025 76.535 1.00 0.00 xxxx 1964 ATOM 1965 CD GLN A 261 82.627 −4.079 77.569 1.00 0.00 xxxx 1965 ATOM 1966 OE1 GLN A 261 83.322 −3.172 78.048 1.00 0.00 xxxx 1966 ATOM 1967 NE2 GLN A 261 81.361 −4.287 77.928 1.00 0.00 xxxx 1967 ATOM 1968 N ALA A 262 86.022 −8.615 77.350 1.00 0.00 xxxx 1968 ATOM 1969 CA ALA A 262 87.239 −9.362 77.682 1.00 0.00 xxxx 1969 ATOM 1970 C ALA A 262 87.835 −10.048 76.459 1.00 0.00 xxxx 1970 ATOM 1971 O ALA A 262 89.052 −10.010 76.237 1.00 0.00 xxxx 1971 ATOM 1972 CB ALA A 262 86.955 −10.397 78.744 1.00 0.00 xxxx 1972 ATOM 1973 N LYS A 263 86.970 −10.684 75.672 1.00 0.00 xxxx 1973 ATOM 1974 CA LYS A 263 87.416 −11.447 74.515 1.00 0.00 xxxx 1974 ATOM 1975 C LYS A 263 88.009 −10.539 73.440 1.00 0.00 xxxx 1975 ATOM 1976 O LYS A 263 89.046 −10.860 72.858 1.00 0.00 xxxx 1976 ATOM 1977 CB LYS A 263 86.259 −12.264 73.932 1.00 0.00 xxxx 1977 ATOM 1978 CG LYS A 263 86.690 −13.251 72.851 1.00 0.00 xxxx 1978 ATOM 1979 CD LYS A 263 87.848 −14.112 73.339 1.00 0.00 xxxx 1979 ATOM 1980 CE LYS A 263 88.295 −15.120 72.290 1.00 0.00 xxxx 1980 ATOM 1981 NZ LYS A 263 89.591 −15.754 72.673 1.00 0.00 xxxx 1981 ATOM 1982 N ALA A 264 87.346 −9.415 73.170 1.00 0.00 xxxx 1982 ATOM 1983 CA ALA A 264 87.865 −8.451 72.197 1.00 0.00 xxxx 1983 ATOM 1984 C ALA A 264 89.197 −7.862 72.657 1.00 0.00 xxxx 1984 ATOM 1985 O ALA A 264 90.134 −7.739 71.857 1.00 0.00 xxxx 1985 ATOM 1986 CB ALA A 264 86.854 −7.334 71.958 1.00 0.00 xxxx 1986 ATOM 1987 N THR A 265 89.288 −7.509 73.937 1.00 0.00 xxxx 1987 ATOM 1988 CA THR A 265 90.530 −6.975 74.485 1.00 0.00 xxxx 1988 ATOM 1989 C THR A 265 91.656 −7.994 74.318 1.00 0.00 xxxx 1989 ATOM 1990 O THR A 265 92.733 −7.662 73.813 1.00 0.00 xxxx 1990 ATOM 1991 CB THR A 265 90.350 −6.589 75.958 1.00 0.00 xxxx 1991 ATOM 1992 OG1 THR A 265 89.369 −5.554 76.042 1.00 0.00 xxxx 1992 ATOM 1993 CG2 THR A 265 91.662 −6.075 76.577 1.00 0.00 xxxx 1993 ATOM 1994 N PHE A 266 91.393 −9.243 74.688 1.00 0.00 xxxx 1994 ATOM 1995 CA PHE A 266 92.401 −10.285 74.533 1.00 0.00 xxxx 1995 ATOM 1996 C PHE A 266 92.778 −10.530 73.063 1.00 0.00 xxxx 1996 ATOM 1997 O PHE A 266 93.968 −10.657 72.742 1.00 0.00 xxxx 1997 ATOM 1998 CB PHE A 266 91.942 −11.607 75.163 1.00 0.00 xxxx 1998 ATOM 1999 CG PHE A 266 92.949 −12.702 75.008 1.00 0.00 xxxx 1999 ATOM 2000 CD1 PHE A 266 94.016 −12.804 75.883 1.00 0.00 xxxx 2000 ATOM 2001 CD2 PHE A 266 92.858 −13.593 73.959 1.00 0.00 xxxx 2001 ATOM 2002 CE1 PHE A 266 94.970 −13.800 75.724 1.00 0.00 xxxx 2002 ATOM 2003 CE2 PHE A 266 93.813 −14.595 73.789 1.00 0.00 xxxx 2003 ATOM 2004 CZ PHE A 266 94.864 −14.688 74.679 1.00 0.00 xxxx 2004 ATOM 2005 N ASP A 267 91.780 −10.616 72.181 1.00 0.00 xxxx 2005 ATOM 2006 CA ASP A 267 92.046 −10.959 70.785 1.00 0.00 xxxx 2006 ATOM 2007 C ASP A 267 92.907 −9.884 70.132 1.00 0.00 xxxx 2007 ATOM 2008 O ASP A 267 93.848 −10.181 69.389 1.00 0.00 xxxx 2008 ATOM 2009 CB ASP A 267 90.743 −11.105 69.995 1.00 0.00 xxxx 2009 ATOM 2010 CG ASP A 267 89.994 −12.396 70.299 1.00 0.00 xxxx 2010 ATOM 2011 OD1 ASP A 267 90.559 −13.321 70.923 1.00 0.00 xxxx 2011 ATOM 2012 OD2 ASP A 267 88.826 −12.487 69.876 1.00 0.00 xxxx 2012 ATOM 2013 N LEU A 268 92.549 −8.632 70.388 1.00 0.00 xxxx 2013 ATOM 2014 CA LEU A 268 93.291 −7.518 69.797 1.00 0.00 xxxx 2014 ATOM 2015 C LEU A 268 94.706 −7.476 70.360 1.00 0.00 xxxx 2015 ATOM 2016 O LEU A 268 95.670 −7.316 69.614 1.00 0.00 xxxx 2016 ATOM 2017 CB LEU A 268 92.593 −6.175 70.054 1.00 0.00 xxxx 2017 ATOM 2018 CG LEU A 268 91.587 −5.752 68.976 1.00 0.00 xxxx 2018 ATOM 2019 CD1 LEU A 268 90.516 −6.801 68.720 1.00 0.00 xxxx 2019 ATOM 2020 CD2 LEU A 268 90.943 −4.413 69.351 1.00 0.00 xxxx 2020 ATOM 2021 N ALA A 269 94.841 −7.635 71.673 1.00 0.00 xxxx 2021 ATOM 2022 CA ALA A 269 96.166 −7.604 72.289 1.00 0.00 xxxx 2022 ATOM 2023 C ALA A 269 97.052 −8.722 71.752 1.00 0.00 xxxx 2023 ATOM 2024 O ALA A 269 98.217 −8.486 71.430 1.00 0.00 xxxx 2024 ATOM 2025 CB ALA A 269 96.046 −7.696 73.795 1.00 0.00 xxxx 2025 ATOM 2026 N LYS A 270 96.498 −9.927 71.627 1.00 0.00 xxxx 2026 ATOM 2027 CA LYS A 270 97.277 −11.069 71.131 1.00 0.00 xxxx 2027 ATOM 2028 C LYS A 270 97.678 −10.875 69.665 1.00 0.00 xxxx 2028 ATOM 2029 O LYS A 270 98.828 −11.149 69.297 1.00 0.00 xxxx 2029 ATOM 2030 CB LYS A 270 96.484 −12.377 71.325 1.00 0.00 xxxx 2030 ATOM 2031 CG LYS A 270 97.152 −13.678 70.800 1.00 0.00 xxxx 2031 ATOM 2032 CD LYS A 270 98.569 −13.884 71.306 1.00 0.00 xxxx 2032 ATOM 2033 CE LYS A 270 99.013 −15.346 71.115 1.00 0.00 xxxx 2033 ATOM 2034 NZ LYS A 270 98.873 −15.867 69.718 1.00 0.00 xxxx 2034 ATOM 2035 N ASN A 271 96.752 −10.396 68.830 1.00 0.00 xxxx 2035 ATOM 2036 CA ASN A 271 97.104 −10.119 67.433 1.00 0.00 xxxx 2036 ATOM 2037 C ASN A 271 98.197 −9.061 67.332 1.00 0.00 xxxx 2037 ATOM 2038 O ASN A 271 99.155 −9.216 66.560 1.00 0.00 xxxx 2038 ATOM 2039 CB ASN A 271 95.880 −9.661 66.643 1.00 0.00 xxxx 2039 ATOM 2040 CG ASN A 271 95.079 −10.814 66.078 1.00 0.00 xxxx 2040 ATOM 2041 OD1 ASN A 271 95.622 −11.879 65.774 1.00 0.00 xxxx 2041 ATOM 2042 ND2 ASN A 271 93.778 −10.592 65.903 1.00 0.00 xxxx 2042 ATOM 2043 N LEU A 272 98.069 −8.000 68.120 1.00 0.00 xxxx 2043 ATOM 2044 CA LEU A 272 99.074 −6.935 68.080 1.00 0.00 xxxx 2044 ATOM 2045 C LEU A 272 100.412 −7.448 68.626 1.00 0.00 xxxx 2045 ATOM 2046 O LEU A 272 101.483 −7.126 68.080 1.00 0.00 xxxx 2046 ATOM 2047 CB LEU A 272 98.574 −5.719 68.853 1.00 0.00 xxxx 2047 ATOM 2048 CG LEU A 272 97.416 −5.022 68.138 1.00 0.00 xxxx 2048 ATOM 2049 CD1 LEU A 272 96.725 −4.072 69.117 1.00 0.00 xxxx 2049 ATOM 2050 CD2 LEU A 272 97.875 −4.262 66.893 1.00 0.00 xxxx 2050 ATOM 2051 N ALA A 273 100.373 −8.263 69.681 1.00 0.00 xxxx 2051 ATOM 2052 CA ALA A 273 101.606 −8.878 70.188 1.00 0.00 xxxx 2052 ATOM 2053 C ALA A 273 102.310 −9.679 69.093 1.00 0.00 xxxx 2053 ATOM 2054 O ALA A 273 103.544 −9.724 69.024 1.00 0.00 xxxx 2054 ATOM 2055 CB ALA A 273 101.302 −9.785 71.385 1.00 0.00 xxxx 2055 ATOM 2056 N ASP A 274 101.506 −10.311 68.240 1.00 0.00 xxxx 2056 ATOM 2057 CA ASP A 274 102.014 −11.193 67.195 1.00 0.00 xxxx 2057 ATOM 2058 C ASP A 274 102.445 −10.407 65.958 1.00 0.00 xxxx 2058 ATOM 2059 O ASP A 274 102.948 −10.989 64.988 1.00 0.00 xxxx 2059 ATOM 2060 CB ASP A 274 100.951 −12.229 66.796 1.00 0.00 xxxx 2060 ATOM 2061 CG ASP A 274 100.725 −13.303 67.854 1.00 0.00 xxxx 2061 ATOM 2062 OD1 ASP A 274 101.565 −13.470 68.771 1.00 0.00 xxxx 2062 ATOM 2063 OD2 ASP A 274 99.701 −14.013 67.747 1.00 0.00 xxxx 2063 ATOM 2064 N GLY A 275 102.244 −9.094 65.978 1.00 0.00 xxxx 2064 ATOM 2065 CA GLY A 275 102.602 −8.263 64.843 1.00 0.00 xxxx 2065 ATOM 2066 C GLY A 275 101.597 −8.298 63.706 1.00 0.00 xxxx 2066 ATOM 2067 O GLY A 275 101.895 −7.887 62.570 1.00 0.00 xxxx 2067 ATOM 2068 N LYS A 276 100.398 −8.797 64.002 1.00 0.00 xxxx 2068 ATOM 2069 CA LYS A 276 99.324 −8.872 63.018 1.00 0.00 xxxx 2069 ATOM 2070 C LYS A 276 98.397 −7.670 63.100 1.00 0.00 xxxx 2070 ATOM 2071 O LYS A 276 98.509 −6.852 64.015 1.00 0.00 xxxx 2071 ATOM 2072 CB LYS A 276 98.504 −10.146 63.207 1.00 0.00 xxxx 2072 ATOM 2073 CG LYS A 276 99.297 −11.425 63.092 1.00 0.00 xxxx 2073 ATOM 2074 CD LYS A 276 98.417 −12.580 63.509 1.00 0.00 xxxx 2074 ATOM 2075 CE LYS A 276 99.157 −13.890 63.440 1.00 0.00 xxxx 2075 ATOM 2076 NZ LYS A 276 98.229 −15.011 63.774 1.00 0.00 xxxx 2076 ATOM 2077 N GLY A 277 97.474 −7.581 62.143 1.00 0.00 xxxx 2077 ATOM 2078 CA GLY A 277 96.403 −6.605 62.226 1.00 0.00 xxxx 2078 ATOM 2079 C GLY A 277 95.544 −6.908 63.435 1.00 0.00 xxxx 2079 ATOM 2080 O GLY A 277 95.335 −8.070 63.769 1.00 0.00 xxxx 2080 ATOM 2081 N ALA A 278 95.058 −5.866 64.095 1.00 0.00 xxxx 2081 ATOM 2082 CA ALA A 278 94.383 −6.019 65.376 1.00 0.00 xxxx 2082 ATOM 2083 C ALA A 278 93.204 −6.995 65.344 1.00 0.00 xxxx 2083 ATOM 2084 O ALA A 278 93.006 −7.747 66.303 1.00 0.00 xxxx 2084 ATOM 2085 CB ALA A 278 93.915 −4.652 65.881 1.00 0.00 xxxx 2085 ATOM 2086 N ALA A 279 92.432 −6.986 64.256 1.00 0.00 xxxx 2086 ATOM 2087 CA ALA A 279 91.224 −7.808 64.177 1.00 0.00 xxxx 2087 ATOM 2088 C ALA A 279 91.413 −9.072 63.342 1.00 0.00 xxxx 2088 ATOM 2089 O ALA A 279 90.444 −9.783 63.071 1.00 0.00 xxxx 2089 ATOM 2090 CB ALA A 279 90.071 −6.989 63.612 1.00 0.00 xxxx 2090 ATOM 2091 N ASP A 280 92.650 −9.355 62.949 1.00 0.00 xxxx 2091 ATOM 2092 CA ASP A 280 92.942 −10.490 62.077 1.00 0.00 xxxx 2092 ATOM 2093 C ASP A 280 92.365 −11.800 62.633 1.00 0.00 xxxx 2093 ATOM 2094 O ASP A 280 92.561 −12.136 63.802 1.00 0.00 xxxx 2094 ATOM 2095 CB ASP A 280 94.454 −10.610 61.864 1.00 0.00 xxxx 2095 ATOM 2096 CG ASP A 280 95.004 −9.556 60.903 1.00 0.00 xxxx 2096 ATOM 2097 OD1 ASP A 280 94.263 −8.604 60.560 1.00 0.00 xxxx 2097 ATOM 2098 OD2 ASP A 280 96.184 −9.677 60.491 1.00 0.00 xxxx 2098 ATOM 2099 N GLY A 281 91.611 −12.511 61.802 1.00 0.00 xxxx 2099 ATOM 2100 CA GLY A 281 91.057 −13.796 62.188 1.00 0.00 xxxx 2100 ATOM 2101 C GLY A 281 89.859 −13.718 63.117 1.00 0.00 xxxx 2101 ATOM 2102 O GLY A 281 89.405 −14.734 63.649 1.00 0.00 xxxx 2102 ATOM 2103 N THR A 282 89.338 −12.511 63.313 1.00 0.00 xxxx 2103 ATOM 2104 CA THR A 282 88.194 −12.309 64.193 1.00 0.00 xxxx 2104 ATOM 2105 C THR A 282 87.072 −11.603 63.460 1.00 0.00 xxxx 2105 ATOM 2106 O THR A 282 87.253 −11.154 62.333 1.00 0.00 xxxx 2106 ATOM 2107 CB THR A 282 88.542 −11.459 65.418 1.00 0.00 xxxx 2107 ATOM 2108 OG1 THR A 282 88.572 −10.079 65.029 1.00 0.00 xxxx 2108 ATOM 2109 CG2 THR A 282 89.899 −11.850 65.993 1.00 0.00 xxxx 2109 ATOM 2110 N ASN A 283 85.923 −11.488 64.117 1.00 0.00 xxxx 2110 ATOM 2111 CA ASN A 283 84.809 −10.731 63.558 1.00 0.00 xxxx 2111 ATOM 2112 C ASN A 283 84.590 −9.426 64.305 1.00 0.00 xxxx 2112 ATOM 2113 O ASN A 283 83.523 −8.824 64.199 1.00 0.00 xxxx 2113 ATOM 2114 CB ASN A 283 83.525 −11.561 63.574 1.00 0.00 xxxx 2114 ATOM 2115 CG ASN A 283 83.481 −12.583 62.453 1.00 0.00 xxxx 2115 ATOM 2116 OD1 ASN A 283 83.915 −12.311 61.331 1.00 0.00 xxxx 2116 ATOM 2117 ND2 ASN A 283 82.959 −13.768 62.751 1.00 0.00 xxxx 2117 ATOM 2118 N TRP A 284 85.595 −8.977 65.059 1.00 0.00 xxxx 2118 ATOM 2119 CA TRP A 284 85.470 −7.704 65.755 1.00 0.00 xxxx 2119 ATOM 2120 C TRP A 284 85.444 −6.558 64.757 1.00 0.00 xxxx 2120 ATOM 2121 O TRP A 284 86.250 −6.505 63.823 1.00 0.00 xxxx 2121 ATOM 2122 CB TRP A 284 86.608 −7.493 66.762 1.00 0.00 xxxx 2122 ATOM 2123 CG TRP A 284 86.637 −8.542 67.829 1.00 0.00 xxxx 2123 ATOM 2124 CD1 TRP A 284 87.626 −9.461 68.055 1.00 0.00 xxxx 2124 ATOM 2125 CD2 TRP A 284 85.610 −8.815 68.793 1.00 0.00 xxxx 2125 ATOM 2126 NE1 TRP A 284 87.278 −10.280 69.101 1.00 0.00 xxxx 2126 ATOM 2127 CE2 TRP A 284 86.047 −9.900 69.574 1.00 0.00 xxxx 2127 ATOM 2128 CE3 TRP A 284 84.360 −8.242 69.069 1.00 0.00 xxxx 2128 ATOM 2129 CZ2 TRP A 284 85.283 −10.432 70.607 1.00 0.00 xxxx 2129 ATOM 2130 CZ3 TRP A 284 83.605 −8.766 70.106 1.00 0.00 xxxx 2130 ATOM 2131 CH2 TRP A 284 84.069 −9.846 70.861 1.00 0.00 xxxx 2131 ATOM 2132 N LYS A 285 84.499 −5.649 64.971 1.00 0.00 xxxx 2132 ATOM 2133 CA LYS A 285 84.365 −4.451 64.160 1.00 0.00 xxxx 2133 ATOM 2134 C LYS A 285 85.161 −3.326 64.800 1.00 0.00 xxxx 2134 ATOM 2135 O LYS A 285 84.763 −2.787 65.829 1.00 0.00 xxxx 2135 ATOM 2136 CB LYS A 285 82.895 −4.057 64.030 1.00 0.00 xxxx 2136 ATOM 2137 CG LYS A 285 82.649 −2.809 63.208 1.00 0.00 xxxx 2137 ATOM 2138 CD LYS A 285 81.294 −2.189 63.538 1.00 0.00 xxxx 2138 ATOM 2139 CE LYS A 285 80.195 −3.244 63.631 1.00 0.00 xxxx 2139 ATOM 2140 NZ LYS A 285 80.057 −4.036 62.376 1.00 0.00 xxxx 2140 ATOM 2141 N ILE A 286 86.301 −2.995 64.206 1.00 0.00 xxxx 2141 ATOM 2142 CA ILE A 286 87.124 −1.913 64.718 1.00 0.00 xxxx 2142 ATOM 2143 C ILE A 286 86.816 −0.677 63.901 1.00 0.00 xxxx 2143 ATOM 2144 O ILE A 286 86.990 −0.675 62.677 1.00 0.00 xxxx 2144 ATOM 2145 CB ILE A 286 88.618 −2.254 64.662 1.00 0.00 xxxx 2145 ATOM 2146 CGI ILE A 286 88.915 −3.557 65.408 1.00 0.00 xxxx 2146 ATOM 2147 CG2 ILE A 286 89.437 −1.152 65.286 1.00 0.00 xxxx 2147 ATOM 2148 CD1 ILE A 286 90.402 −3.902 65.442 1.00 0.00 xxxx 2148 ATOM 2149 N ASP A 287 86.329 0.363 64.570 1.00 0.00 xxxx 2149 ATOM 2150 CA ASP A 287 86.022 1.631 63.916 1.00 0.00 xxxx 2150 ATOM 2151 C ASP A 287 86.955 2.709 64.451 1.00 0.00 xxxx 2151 ATOM 2152 O ASP A 287 86.837 3.105 65.616 1.00 0.00 xxxx 2152 ATOM 2153 CB ASP A 287 84.563 2.017 64.150 1.00 0.00 xxxx 2153 ATOM 2154 CG ASP A 287 84.222 3.391 63.604 1.00 0.00 xxxx 2154 ATOM 2155 OD1 ASP A 287 83.193 3.952 64.034 1.00 0.00 xxxx 2155 ATOM 2156 OD2 ASP A 287 84.976 3.911 62.754 1.00 0.00 xxxx 2156 ATOM 2157 N ASN A 288 87.874 3.167 63.603 1.00 0.00 xxxx 2157 ATOM 2158 CA ASN A 288 88.884 4.149 63.997 1.00 0.00 xxxx 2158 ATOM 2159 C ASN A 288 89.522 3.727 65.319 1.00 0.00 xxxx 2159 ATOM 2160 O ASN A 288 89.561 4.490 66.282 1.00 0.00 xxxx 2160 ATOM 2161 CB ASN A 288 88.279 5.547 64.118 1.00 0.00 xxxx 2161 ATOM 2162 CG ASN A 288 89.326 6.645 64.007 1.00 0.00 xxxx 2162 ATOM 2163 OD1 ASN A 288 90.478 6.391 63.649 1.00 0.00 xxxx 2163 ATOM 2164 ND2 ASN A 288 88.926 7.874 64.312 1.00 0.00 xxxx 2164 ATOM 2165 N LYS A 289 89.969 2.475 65.337 1.00 0.00 xxxx 2165 ATOM 2166 CA LYS A 289 90.722 1.852 66.426 1.00 0.00 xxxx 2166 ATOM 2167 C LYS A 289 89.913 1.565 67.685 1.00 0.00 xxxx 2167 ATOM 2168 O LYS A 289 90.494 1.252 68.706 1.00 0.00 xxxx 2168 ATOM 2169 CB LYS A 289 91.943 2.703 66.761 1.00 0.00 xxxx 2169 ATOM 2170 CG LYS A 289 92.803 2.945 65.519 1.00 0.00 xxxx 2170 ATOM 2171 CD LYS A 289 94.224 3.241 65.877 1.00 0.00 xxxx 2171 ATOM 2172 CE LYS A 289 94.317 4.511 66.697 1.00 0.00 xxxx 2172 ATOM 2173 NZ LYS A 289 95.738 4.684 67.101 1.00 0.00 xxxx 2173 ATOM 2174 N VAL A 290 88.585 1.619 67.581 1.00 0.00 xxxx 2174 ATOM 2175 CA VAL A 290 87.691 1.387 68.712 1.00 0.00 xxxx 2175 ATOM 2176 C VAL A 290 86.720 0.237 68.435 1.00 0.00 xxxx 2176 ATOM 2177 O VAL A 290 86.116 0.171 67.356 1.00 0.00 xxxx 2177 ATOM 2178 CB VAL A 290 86.903 2.664 69.053 1.00 0.00 xxxx 2178 ATOM 2179 CG1 VAL A 290 85.925 2.394 70.204 1.00 0.00 xxxx 2179 ATOM 2180 CG2 VAL A 290 87.847 3.824 69.381 1.00 0.00 xxxx 2180 ATOM 2181 N VAL A 291 86.578 −0.658 69.414 1.00 0.00 xxxx 2181 ATOM 2182 CA VAL A 291 85.515 −1.666 69.437 1.00 0.00 xxxx 2182 ATOM 2183 C VAL A 291 84.489 −1.292 70.498 1.00 0.00 xxxx 2183 ATOM 2184 O VAL A 291 84.852 −1.110 71.657 1.00 0.00 xxxx 2184 ATOM 2185 CB VAL A 291 86.066 −3.066 69.726 1.00 0.00 xxxx 2185 ATOM 2186 CG1 VAL A 291 84.922 −4.078 69.847 1.00 0.00 xxxx 2186 ATOM 2187 CG2 VAL A 291 87.077 −3.484 68.661 1.00 0.00 xxxx 2187 ATOM 2188 N ARG A 292 83.218 −1.198 70.124 1.00 0.00 xxxx 2188 ATOM 2189 CA ARG A 292 82.153 −0.990 71.106 1.00 0.00 xxxx 2189 ATOM 2190 C ARG A 292 81.193 −2.177 71.103 1.00 0.00 xxxx 2190 ATOM 2191 O ARG A 292 80.611 −2.524 70.072 1.00 0.00 xxxx 2191 ATOM 2192 CB ARG A 292 81.410 0.318 70.830 1.00 0.00 xxxx 2192 ATOM 2193 CG ARG A 292 82.339 1.527 70.900 1.00 0.00 xxxx 2193 ATOM 2194 CD ARG A 292 81.619 2.864 70.873 1.00 0.00 xxxx 2194 ATOM 2195 NE ARG A 292 82.583 3.942 70.642 1.00 0.00 xxxx 2195 ATOM 2196 CZ ARG A 292 83.265 4.572 71.597 1.00 0.00 xxxx 2196 ATOM 2197 NH1 ARG A 292 83.082 4.260 72.880 1.00 0.00 xxxx 2197 ATOM 2198 NH2 ARG A 292 84.133 5.524 71.270 1.00 0.00 xxxx 2198 ATOM 2199 N VAL A 293 81.035 −2.795 72.270 1.00 0.00 xxxx 2199 ATOM 2200 CA VAL A 293 80.206 −3.979 72.446 1.00 0.00 xxxx 2200 ATOM 2201 C VAL A 293 78.823 −3.541 72.921 1.00 0.00 xxxx 2201 ATOM 2202 O VAL A 293 78.716 −2.749 73.854 1.00 0.00 xxxx 2202 ATOM 2203 CB VAL A 293 80.868 −4.953 73.451 1.00 0.00 xxxx 2203 ATOM 2204 CG1 VAL A 293 80.007 −6.186 73.661 1.00 0.00 xxxx 2204 ATOM 2205 CG2 VAL A 293 82.286 −5.342 72.966 1.00 0.00 xxxx 2205 ATOM 2206 N PRO A 294 77.763 −4.028 72.264 1.00 0.00 xxxx 2206 ATOM 2207 CA PRO A 294 76.400 −3.585 72.591 1.00 0.00 xxxx 2207 ATOM 2208 C PRO A 294 75.942 −3.913 74.009 1.00 0.00 xxxx 2208 ATOM 2209 O PRO A 294 76.295 −4.954 74.569 1.00 0.00 xxxx 2209 ATOM 2210 CB PRO A 294 75.530 −4.347 71.592 1.00 0.00 xxxx 2210 ATOM 2211 CG PRO A 294 76.441 −4.689 70.475 1.00 0.00 xxxx 2211 ATOM 2212 CD PRO A 294 77.791 −4.917 71.094 1.00 0.00 xxxx 2212 ATOM 2213 N TYR A 295 75.146 −3.004 74.563 1.00 0.00 xxxx 2213 ATOM 2214 CA TYR A 295 74.359 −3.271 75.761 1.00 0.00 xxxx 2214 ATOM 2215 C TYR A 295 73.038 −3.956 75.407 1.00 0.00 xxxx 2215 ATOM 2216 O TYR A 295 72.542 −3.815 74.291 1.00 0.00 xxxx 2216 ATOM 2217 CB TYR A 295 74.047 −1.974 76.497 1.00 0.00 xxxx 2217 ATOM 2218 CG TYR A 295 75.211 −1.244 77.128 1.00 0.00 xxxx 2218 ATOM 2219 CD1 TYR A 295 75.657 −1.576 78.401 1.00 0.00 xxxx 2219 ATOM 2220 CD2 TYR A 295 75.805 −0.160 76.490 1.00 0.00 xxxx 2220 ATOM 2221 CE1 TYR A 295 76.699 −0.880 79.010 1.00 0.00 xxxx 2221 ATOM 2222 CE2 TYR A 295 76.839 0.540 77.088 1.00 0.00 xxxx 2222 ATOM 2223 CZ TYR A 295 77.287 0.179 78.349 1.00 0.00 xxxx 2223 ATOM 2224 OH TYR A 295 78.304 0.888 78.944 1.00 0.00 xxxx 2224 ATOM 2225 N VAL A 296 72.448 −4.668 76.368 1.00 0.00 xxxx 2225 ATOM 2226 CA VAL A 296 71.141 −5.312 76.180 1.00 0.00 xxxx 2226 ATOM 2227 C VAL A 296 70.270 −5.142 77.430 1.00 0.00 xxxx 2227 ATOM 2228 O VAL A 296 70.722 −5.438 78.526 1.00 0.00 xxxx 2228 ATOM 2229 CB VAL A 296 71.290 −6.820 75.854 1.00 0.00 xxxx 2229 ATOM 2230 CG1 VAL A 296 69.929 −7.427 75.553 1.00 0.00 xxxx 2230 ATOM 2231 CG2 VAL A 296 72.262 −7.048 74.700 1.00 0.00 xxxx 2231 ATOM 2232 N GLY A 297 69.024 −4.691 77.273 1.00 0.00 xxxx 2232 ATOM 2233 CA GLY A 297 68.127 −4.557 78.417 1.00 0.00 xxxx 2233 ATOM 2234 C GLY A 297 67.730 −5.896 79.010 1.00 0.00 xxxx 2234 ATOM 2235 O GLY A 297 67.462 −6.840 78.271 1.00 0.00 xxxx 2235 ATOM 2236 N VAL A 298 67.682 −5.980 80.341 1.00 0.00 xxxx 2236 ATOM 2237 CA VAL A 298 67.368 −7.232 81.032 1.00 0.00 xxxx 2237 ATOM 2238 C VAL A 298 66.268 −7.038 82.073 1.00 0.00 xxxx 2238 ATOM 2239 O VAL A 298 66.392 −6.199 82.965 1.00 0.00 xxxx 2239 ATOM 2240 CB VAL A 298 68.630 −7.827 81.717 1.00 0.00 xxxx 2240 ATOM 2241 CG1 VAL A 298 68.279 −9.124 82.444 1.00 0.00 xxxx 2241 ATOM 2242 CG2 VAL A 298 69.751 −8.070 80.706 1.00 0.00 xxxx 2242 ATOM 2243 N ASP A 299 65.203 −7.826 81.982 1.00 0.00 xxxx 2243 ATOM 2244 CA ASP A 299 64.227 −7.885 83.067 1.00 0.00 xxxx 2244 ATOM 2245 C ASP A 299 63.676 −9.302 83.204 1.00 0.00 xxxx 2245 ATOM 2246 O ASP A 299 64.224 −10.238 82.626 1.00 0.00 xxxx 2246 ATOM 2247 CB ASP A 299 63.100 −6.871 82.852 1.00 0.00 xxxx 2247 ATOM 2248 CG ASP A 299 62.370 −7.052 81.526 1.00 0.00 xxxx 2248 ATOM 2249 OD1 ASP A 299 62.441 −8.141 80.921 1.00 0.00 xxxx 2249 ATOM 2250 OD2 ASP A 299 61.711 −6.090 81.088 1.00 0.00 xxxx 2250 ATOM 2251 N LYS A 300 62.601 −9.459 83.969 1.00 0.00 xxxx 2251 ATOM 2252 CA LYS A 300 62.028 −10.784 84.188 1.00 0.00 xxxx 2252 ATOM 2253 C LYS A 300 61.629 −11.480 82.887 1.00 0.00 xxxx 2253 ATOM 2254 O LYS A 300 61.693 −12.708 82.795 1.00 0.00 xxxx 2254 ATOM 2255 CB LYS A 300 60.817 −10.692 85.117 1.00 0.00 xxxx 2255 ATOM 2256 CG LYS A 300 61.178 −10.695 86.589 1.00 0.00 xxxx 2256 ATOM 2257 CD LYS A 300 59.943 −10.846 87.458 1.00 0.00 xxxx 2257 ATOM 2258 CE LYS A 300 60.317 −11.060 88.913 1.00 0.00 xxxx 2258 ATOM 2259 NZ LYS A 300 59.113 −11.141 89.790 1.00 0.00 xxxx 2259 ATOM 2260 N ASP A 301 61.237 −10.703 81.881 1.00 0.00 xxxx 2260 ATOM 2261 CA ASP A 301 60.716 −11.282 80.637 1.00 0.00 xxxx 2261 ATOM 2262 C ASP A 301 61.778 −12.014 79.811 1.00 0.00 xxxx 2262 ATOM 2263 O ASP A 301 61.472 −13.011 79.157 1.00 0.00 xxxx 2263 ATOM 2264 CB ASP A 301 60.063 −10.203 79.770 1.00 0.00 xxxx 2264 ATOM 2265 CG ASP A 301 58.783 −9.660 80.375 1.00 0.00 xxxx 2265 ATOM 2266 OD1 ASP A 301 58.198 −10.330 81.253 1.00 0.00 xxxx 2266 ATOM 2267 OD2 ASP A 301 58.354 −8.562 79.961 1.00 0.00 xxxx 2267 ATOM 2268 N ASN A 302 63.016 −11.527 79.825 1.00 0.00 xxxx 2268 ATOM 2269 CA ASN A 302 64.069 −12.161 79.033 1.00 0.00 xxxx 2269 ATOM 2270 C ASN A 302 65.214 −12.678 79.899 1.00 0.00 xxxx 2270 ATOM 2271 O ASN A 302 66.301 −12.953 79.397 1.00 0.00 xxxx 2271 ATOM 2272 CB ASN A 302 64.607 −11.195 77.961 1.00 0.00 xxxx 2272 ATOM 2273 CG ASN A 302 65.396 −10.021 78.546 1.00 0.00 xxxx 2273 ATOM 2274 OD1 ASN A 302 65.258 −9.690 79.720 1.00 0.00 xxxx 2274 ATOM 2275 ND2 ASN A 302 66.218 −9.383 77.714 1.00 0.00 xxxx 2275 ATOM 2276 N LEU A 303 64.950 −12.842 81.192 1.00 0.00 xxxx 2276 ATOM 2277 CA LEU A 303 65.989 −13.194 82.159 1.00 0.00 xxxx 2277 ATOM 2278 C LEU A 303 66.640 −14.545 81.863 1.00 0.00 xxxx 2278 ATOM 2279 O LEU A 303 67.844 −14.722 82.055 1.00 0.00 xxxx 2279 ATOM 2280 CB LEU A 303 65.406 −13.204 83.575 1.00 0.00 xxxx 2280 ATOM 2281 CG LEU A 303 66.412 −13.453 84.698 1.00 0.00 xxxx 2281 ATOM 2282 CD1 LEU A 303 67.491 −12.378 84.690 1.00 0.00 xxxx 2282 ATOM 2283 CD2 LEU A 303 65.705 −13.529 86.046 1.00 0.00 xxxx 2283 ATOM 2284 N ALA A 304 65.835 −15.486 81.382 1.00 0.00 xxxx 2284 ATOM 2285 CA ALA A 304 66.295 −16.847 81.119 1.00 0.00 xxxx 2285 ATOM 2286 C ALA A 304 67.334 −16.907 79.999 1.00 0.00 xxxx 2286 ATOM 2287 O ALA A 304 68.003 −17.926 79.822 1.00 0.00 xxxx 2287 ATOM 2288 CB ALA A 304 65.110 −17.741 80.783 1.00 0.00 xxxx 2288 ATOM 2289 O GLU A 305 70.668 −15.086 77.723 1.00 0.00 xxxx 2289 ATOM 2290 N GLU A 305 67.465 −15.817 79.248 1.00 0.00 xxxx 2290 ATOM 2291 CA GLU A 305 68.405 −15.758 78.133 1.00 0.00 xxxx 2291 ATOM 2292 C GLU A 305 69.808 −15.338 78.567 1.00 0.00 xxxx 2292 ATOM 2293 CB GLU A 305 67.897 −14.793 77.060 1.00 0.00 xxxx 2293 ATOM 2294 CG GLU A 305 66.535 −15.149 76.491 1.00 0.00 xxxx 2294 ATOM 2295 CD GLU A 305 65.997 −14.081 75.556 1.00 0.00 xxxx 2295 ATOM 2296 OE1 GLU A 305 66.778 −13.194 75.150 1.00 0.00 xxxx 2296 ATOM 2297 OE2 GLU A 305 64.790 −14.124 75.230 1.00 0.00 xxxx 2297 ATOM 2298 N PHE A 306 70.042 −15.263 79.874 1.00 0.00 xxxx 2298 ATOM 2299 CA PHE A 306 71.332 −14.800 80.384 1.00 0.00 xxxx 2299 ATOM 2300 C PHE A 306 71.923 −15.759 81.414 1.00 0.00 xxxx 2300 ATOM 2301 O PHE A 306 71.297 −16.063 82.430 1.00 0.00 xxxx 2301 ATOM 2302 CB PHE A 306 71.190 −13.397 80.983 1.00 0.00 xxxx 2302 ATOM 2303 CG PHE A 306 70.743 −12.366 79.989 1.00 0.00 xxxx 2303 ATOM 2304 CD1 PHE A 306 71.669 −11.643 79.258 1.00 0.00 xxxx 2304 ATOM 2305 CD2 PHE A 306 69.394 −12.139 79.766 1.00 0.00 xxxx 2305 ATOM 2306 CE1 PHE A 306 71.259 −10.703 78.330 1.00 0.00 xxxx 2306 ATOM 2307 CE2 PHE A 306 68.979 −11.206 78.839 1.00 0.00 xxxx 2307 ATOM 2308 CZ PHE A 306 69.912 −10.488 78.118 1.00 0.00 xxxx 2308 ATOM 2309 N SER A 307 73.135 −16.234 81.137 1.00 0.00 xxxx 2309 ATOM 2310 CA SER A 307 73.836 −17.143 82.037 1.00 0.00 xxxx 2310 ATOM 2311 C SER A 307 74.912 −16.399 82.823 1.00 0.00 xxxx 2311 ATOM 2312 O SER A 307 74.852 −15.178 82.974 1.00 0.00 xxxx 2312 ATOM 2313 CB SER A 307 74.460 −18.305 81.257 1.00 0.00 xxxx 2313 ATOM 2314 OG SER A 307 73.468 −19.075 80.596 1.00 0.00 xxxx 2314 HETATM 2315 C2 GLC B 1 92.690 −2.746 98.842 1.00 0.00 xxxx 2315 HETATM 2316 C3 GLC B 1 92.583 −2.324 97.414 1.00 0.00 xxxx 2316 HETATM 2317 C4 GLC B 1 92.596 −3.496 96.471 1.00 0.00 xxxx 2317 HETATM 2318 C5 GLC B 1 91.481 −4.463 96.869 1.00 0.00 xxxx 2318 HETATM 2319 C6 GLC B 1 91.486 −5.686 96.009 1.00 0.00 xxxx 2319 HETATM 2320 C1 GLC B 1 91.608 −3.754 99.186 1.00 0.00 xxxx 2320 HETATM 2321 O1 GLC B 1 91.764 −4.278 100.438 1.00 0.00 xxxx 2321 HETATM 2322 O2 GLC B 1 92.488 −1.602 99.689 1.00 0.00 xxxx 2322 HETATM 2323 O3 GLC B 1 93.663 −1.404 97.079 1.00 0.00 xxxx 2323 HETATM 2324 O4 GLC B 1 92.389 −3.037 95.130 1.00 0.00 xxxx 2324 HETATM 2325 O5 GLC B 1 91.680 −4.901 98.250 1.00 0.00 xxxx 2325 HETATM 2326 O6 GLC B 1 90.408 −6.542 96.329 1.00 0.00 xxxx 2326 HETATM 2327 C2 GLC B 1 83.021 −4.575 97.570 1.00 0.00 xxxx 2327 HETATM 2328 C3 GLC B 1 81.832 −4.206 96.753 1.00 0.00 xxxx 2328 HETATM 2329 C4 GLC B 1 81.920 −2.801 96.215 1.00 0.00 xxxx 2329 HETATM 2330 C5 GLC B 1 83.229 −2.630 95.437 1.00 0.00 xxxx 2330 HETATM 2331 C6 GLC B 1 83.321 −1.238 94.879 1.00 0.00 xxxx 2331 HETATM 2332 C1 GLC B 1 84.339 −4.267 96.878 1.00 0.00 xxxx 2332 HETATM 2333 O1 GLC B 1 85.348 −4.414 97.783 1.00 0.00 xxxx 2333 HETATM 2334 O2 GLC B 1 82.974 −5.984 97.880 1.00 0.00 xxxx 2334 HETATM 2335 O3 GLC B 1 80.691 −4.345 97.633 1.00 0.00 xxxx 2335 HETATM 2336 O4 GLC B 1 80.814 −2.458 95.361 1.00 0.00 xxxx 2336 HETATM 2337 O5 GLC B 1 84.362 −2.867 96.341 1.00 0.00 xxxx 2337 HETATM 2338 O6 GLC B 1 84.340 −1.167 93.916 1.00 0.00 xxxx 2338 HETATM 2339 C2 GLC B 1 80.567 −0.156 84.804 1.00 0.00 xxxx 2339 HETATM 2340 C3 GLC B 1 80.797 0.238 86.214 1.00 0.00 xxxx 2340 HETATM 2341 C4 GLC B 1 82.268 0.274 86.520 1.00 0.00 xxxx 2341 HETATM 2342 C5 GLC B 1 83.019 1.200 85.560 1.00 0.00 xxxx 2342 HETATM 2343 C6 GLC B 1 84.494 1.071 85.797 1.00 0.00 xxxx 2343 HETATM 2344 C1 GLC B 1 81.296 0.784 83.863 1.00 0.00 xxxx 2344 HETATM 2345 O1 GLC B 1 81.119 0.356 82.586 1.00 0.00 xxxx 2345 HETATM 2346 O2 GLC B 1 79.162 −0.097 84.487 1.00 0.00 xxxx 2346 HETATM 2347 O3 GLC B 1 80.162 −0.738 87.080 1.00 0.00 xxxx 2347 HETATM 2348 O4 GLC B 1 82.448 0.724 87.865 1.00 0.00 xxxx 2348 HETATM 2349 O5 GLC B 1 82.760 0.835 84.165 1.00 0.00 xxxx 2349 HETATM 2350 O6 GLC B 1 85.215 1.890 84.906 1.00 0.00 xxxx 2350 HETATM 2351 C01 ACR H 1 89.320 8.265 96.523 1.00 0.00 xxxx 2351 HETATM 2352 N02 ACR H 1 88.307 7.240 96.350 1.00 0.00 xxxx 2352 HETATM 2353 C03 ACR H 1 87.743 6.573 97.511 1.00 0.00 xxxx 2353 HETATM 2354 C04 ACR H 1 87.854 6.877 95.019 1.00 0.00 xxxx 2354 HETATM 2355 C05 ACR H 1 86.887 5.890 94.867 1.00 0.00 xxxx 2355 HETATM 2356 C06 ACR H 1 86.444 5.530 93.561 1.00 0.00 xxxx 2356 HETATM 2357 C07 ACR H 1 86.959 6.149 92.460 1.00 0.00 xxxx 2357 HETATM 2358 C08 ACR H 1 87.951 7.162 92.617 1.00 0.00 xxxx 2358 HETATM 2359 C09 ACR H 1 88.389 7.511 93.893 1.00 0.00 xxxx 2359 HETATM 2360 C10 ACR H 1 86.503 5.785 91.156 1.00 0.00 xxxx 2360 HETATM 2361 C11 ACR H 1 85.537 4.795 91.016 1.00 0.00 xxxx 2361 HETATM 2362 C12 ACR H 1 85.018 4.165 92.145 1.00 0.00 xxxx 2362 HETATM 2363 C13 ACR H 1 85.455 4.521 93.413 1.00 0.00 xxxx 2363 HETATM 2364 C14 ACR H 1 85.016 4.366 89.647 1.00 0.00 xxxx 2364 HETATM 2365 O15 ACR H 1 85.422 4.856 88.645 1.00 0.00 xxxx 2365 HETATM 2366 C16 ACR H 1 83.949 3.277 89.605 1.00 0.00 xxxx 2366 HETATM 2367 C17 ACR H 1 82.796 3.601 88.672 1.00 0.00 xxxx 2367 HETATM 2368 C2 GLC E 1 74.043 3.534 106.784 1.00 0.00 xxxx 2368 HETATM 2369 C3 GLC E 1 73.870 4.007 108.173 1.00 0.00 xxxx 2369 HETATM 2370 C4 GLC E 1 72.769 3.314 108.911 1.00 0.00 xxxx 2370 HETATM 2371 C5 GLC E 1 72.652 1.800 108.679 1.00 0.00 xxxx 2371 HETATM 2372 C6 GLC E 1 71.229 1.409 108.957 1.00 0.00 xxxx 2372 HETATM 2373 C1 GLC E 1 74.196 2.025 106.743 1.00 0.00 xxxx 2373 HETATM 2374 O1 GLC E 1 74.348 1.636 105.448 1.00 0.00 xxxx 2374 HETATM 2375 O2 GLC E 1 75.235 4.143 106.253 1.00 0.00 xxxx 2375 HETATM 2376 O3 GLC E 1 73.539 5.421 108.139 1.00 0.00 xxxx 2376 HETATM 2377 O4 GLC E 1 73.014 3.548 110.299 1.00 0.00 xxxx 2377 HETATM 2378 O5 GLC E 1 72.987 1.347 107.318 1.00 0.00 xxxx 2378 HETATM 2379 O6 GLC E 1 70.837 0.351 108.121 1.00 0.00 xxxx 2379 HETATM 2380 C2 GLC E 1 63.097 −3.500 75.382 1.00 0.00 xxxx 2380 HETATM 2381 C3 GLC E 1 64.434 −4.145 75.413 1.00 0.00 xxxx 2381 HETATM 2382 C4 GLC E 1 64.610 −5.099 76.560 1.00 0.00 xxxx 2382 HETATM 2383 C5 GLC E 1 63.418 −6.043 76.763 1.00 0.00 xxxx 2383 HETATM 2384 C6 GLC E 1 63.551 −6.742 78.085 1.00 0.00 xxxx 2384 HETATM 2385 C1 GLC E 1 61.987 −4.531 75.469 1.00 0.00 xxxx 2385 HETATM 2386 O1 GLC E 1 60.787 −3.891 75.460 1.00 0.00 xxxx 2386 HETATM 2387 O2 GLC E 1 62.942 −2.769 74.151 1.00 0.00 xxxx 2387 HETATM 2388 O3 GLC E 1 65.458 −3.110 75.509 1.00 0.00 xxxx 2388 HETATM 2389 O4 GLC E 1 65.777 −5.887 76.302 1.00 0.00 xxxx 2389 HETATM 2390 O5 GLC E 1 62.124 −5.342 76.723 1.00 0.00 xxxx 2390 HETATM 2391 O6 GLC E 1 62.509 −7.677 78.244 1.00 0.00 xxxx 2391 HETATM 2392 CA CA M 1 54.443 10.528 90.671 1.00 0.00 xxxx 2392 HETATM 2393 O HOH S 1 64.967 12.689 101.419 1.00 0.00 xxxx 2393 HETATM 2394 O HOH S 2 71.563 5.785 84.976 1.00 0.00 xxxx 2394 HETATM 2395 O HOH S 3 80.923 −2.340 89.295 1.00 0.00 xxxx 2395 HETATM 2396 O HOH S 4 56.757 3.515 93.548 1.00 0.00 xxxx 2396 HETATM 2397 O HOH S 5 95.702 −5.521 95.382 1.00 0.00 xxxx 2397 HETATM 2398 O HOH S 6 78.131 −2.907 89.098 1.00 0.00 xxxx 2398 HETATM 2399 O HOH S 7 78.263 −4.245 76.555 1.00 0.00 xxxx 2399 HETATM 2400 O HOH S 8 93.988 −3.398 102.054 1.00 0.00 xxxx 2400 HETATM 2401 O HOH S 9 83.364 2.281 77.076 1.00 0.00 xxxx 2401 HETATM 2402 O HOH S 10 55.561 10.622 95.053 1.00 0.00 xxxx 2402 HETATM 2403 O HOH S 11 56.036 1.251 94.793 1.00 0.00 xxxx 2403 HETATM 2404 O HOH S 12 92.822 10.636 77.633 1.00 0.00 xxxx 2404 HETATM 2405 O HOH S 13 103.721 −4.910 86.930 1.00 0.00 xxxx 2405 HETATM 2406 O HOH S 14 84.655 4.673 79.569 1.00 0.00 xxxx 2406 HETATM 2407 O HOH S 15 86.063 −2.878 78.146 1.00 0.00 xxxx 2407 HETATM 2408 O HOH S 16 63.999 15.452 85.780 1.00 0.00 xxxx 2408 HETATM 2409 O HOH S 17 97.891 −19.300 78.614 1.00 0.00 xxxx 2409 HETATM 2410 O HOH S 18 60.292 16.203 83.158 1.00 0.00 xxxx 2410 HETATM 2411 O HOH S 19 83.019 4.976 77.084 1.00 0.00 xxxx 2411 HETATM 2412 O HOH S 20 78.782 −5.387 95.995 1.00 0.00 xxxx 2412 HETATM 2413 O HOH S 21 82.607 −1.435 80.011 1.00 0.00 xxxx 2413 HETATM 2414 O HOH S 22 63.199 16.555 83.175 1.00 0.00 xxxx 2414 HETATM 2415 O HOH S 23 97.299 −13.937 66.671 1.00 0.00 xxxx 2415 HETATM 2416 O HOH S 24 77.647 −0.308 73.329 1.00 0.00 xxxx 2416 HETATM 2417 O HOH S 25 72.956 6.465 105.943 1.00 0.00 xxxx 2417 HETATM 2418 O HOH S 26 54.476 12.405 82.647 1.00 0.00 xxxx 2418 HETATM 2419 O HOH S 27 103.889 −13.594 65.061 1.00 0.00 xxxx 2419 HETATM 2420 O HOH S 28 69.798 6.225 109.324 1.00 0.00 xxxx 2420 HETATM 2421 O HOH S 29 82.160 −1.182 91.535 1.00 0.00 xxxx 2421 HETATM 2422 O HOH S 30 95.116 −13.976 64.095 1.00 0.00 xxxx 2422 HETATM 2423 O HOH S 31 63.291 −3.325 92.624 1.00 0.00 xxxx 2423 HETATM 2424 O HOH S 32 51.558 16.241 86.760 1.00 0.00 xxxx 2424 HETATM 2425 O HOH S 33 82.692 1.250 79.488 1.00 0.00 xxxx 2425 HETATM 2426 O HOH S 34 58.233 14.653 79.027 1.00 0.00 xxxx 2426 HETATM 2427 O HOH S 35 76.576 −7.589 73.550 1.00 0.00 xxxx 2427 HETATM 2428 O HOH S 36 101.994 −4.603 91.215 1.00 0.00 xxxx 2428 HETATM 2429 O HOH S 37 52.930 8.706 83.603 1.00 0.00 xxxx 2429 HETATM 2430 O HOH S 38 104.304 −4.180 89.612 1.00 0.00 xxxx 2430 HETATM 2431 O HOH S 39 87.731 8.186 72.461 1.00 0.00 xxxx 2431 HETATM 2432 O HOH S 40 63.628 17.345 87.950 1.00 0.00 xxxx 2432 HETATM 2433 O HOH S 41 79.089 −10.881 79.735 1.00 0.00 xxxx 2433 HETATM 2434 O HOH S 42 85.636 −13.717 77.361 1.00 0.00 xxxx 2434 HETATM 2435 O HOH S 43 82.637 −1.836 67.270 1.00 0.00 xxxx 2435 HETATM 2436 O HOH S 44 83.873 −13.593 84.483 1.00 0.00 xxxx 2436 HETATM 2437 O HOH S 45 58.492 6.346 98.905 1.00 0.00 xxxx 2437 HETATM 2438 O HOH S 46 102.773 −0.145 91.513 1.00 0.00 xxxx 2438 HETATM 2439 O HOH S 47 95.927 −3.173 63.290 1.00 0.00 xxxx 2439 HETATM 2440 O HOH S 48 95.651 2.686 96.406 1.00 0.00 xxxx 2440 HETATM 2441 O HOH S 49 94.768 8.045 90.644 1.00 0.00 xxxx 2441 HETATM 2442 O HOH S 50 110.557 −0.277 81.899 1.00 0.00 xxxx 2442 HETATM 2443 O HOH S 51 89.666 −8.773 94.962 1.00 0.00 xxxx 2443 HETATM 2444 O HOH S 52 78.271 11.349 100.263 1.00 0.00 xxxx 2444 HETATM 2445 O HOH S 53 90.013 14.373 72.022 1.00 0.00 xxxx 2445 HETATM 2446 O HOH S 54 54.686 −1.991 79.584 1.00 0.00 xxxx 2446 HETATM 2447 O HOH S 55 54.060 10.208 97.384 1.00 0.00 xxxx 2447 HETATM 2448 O HOH S 56 59.790 16.417 80.364 1.00 0.00 xxxx 2448 HETATM 2449 O HOH S 57 77.401 7.520 100.770 1.00 0.00 xxxx 2449 HETATM 2450 O HOH S 58 51.231 7.595 85.998 1.00 0.00 xxxx 2450 HETATM 2451 O HOH S 59 82.426 −6.107 67.060 1.00 0.00 xxxx 2451 HETATM 2452 O HOH S 60 68.071 −3.957 74.775 1.00 0.00 xxxx 2452 HETATM 2453 O HOH S 61 61.816 −7.423 86.024 1.00 0.00 xxxx 2453 HETATM 2454 O HOH S 62 62.403 −8.118 88.651 1.00 0.00 xxxx 2454 HETATM 2455 O HOH S 63 91.608 −17.642 73.896 1.00 0.00 xxxx 2455 HETATM 2456 O HOH S 64 78.078 −8.136 83.415 1.00 0.00 xxxx 2456 HETATM 2457 O HOH S 65 64.474 −4.069 98.736 1.00 0.00 xxxx 2457 HETATM 2458 O HOH S 66 102.228 10.529 75.052 1.00 0.00 xxxx 2458 HETATM 2459 O HOH S 67 78.259 7.764 74.423 1.00 0.00 xxxx 2459 HETATM 2460 O HOH S 68 50.503 −1.277 89.513 1.00 0.00 xxxx 2460 HETATM 2461 O HOH S 69 104.992 −1.785 90.522 1.00 0.00 xxxx 2461 HETATM 2462 O HOH S 70 91.823 −11.886 88.298 1.00 0.00 xxxx 2462 HETATM 2463 O HOH S 71 99.237 −12.571 86.653 1.00 0.00 xxxx 2463 HETATM 2464 O HOH S 72 55.772 13.625 95.460 1.00 0.00 xxxx 2464 HETATM 2465 O HOH S 73 102.895 6.060 66.290 1.00 0.00 xxxx 2465 HETATM 2466 O HOH S 74 101.101 10.601 72.687 1.00 0.00 xxxx 2466 HETATM 2467 O HOH S 75 90.600 1.190 62.778 1.00 0.00 xxxx 2467 HETATM 2468 O HOH S 76 46.025 12.655 90.998 1.00 0.00 xxxx 2468 HETATM 2469 O HOH S 77 89.016 5.541 89.546 1.00 0.00 xxxx 2469 HETATM 2470 O HOH S 78 55.575 1.314 97.525 1.00 0.00 xxxx 2470 HETATM 2471 O HOH S 79 106.870 −11.908 75.592 1.00 0.00 xxxx 2471 HETATM 2472 O HOH S 80 106.021 5.208 86.640 1.00 0.00 xxxx 2472 HETATM 2473 O HOH S 81 85.474 5.243 66.632 1.00 0.00 xxxx 2473 HETATM 2474 O HOH S 82 108.949 2.324 81.288 1.00 0.00 xxxx 2474 HETATM 2475 O HOH S 83 93.941 −13.080 68.593 1.00 0.00 xxxx 2475 HETATM 2476 O HOH S 84 98.669 11.594 80.048 1.00 0.00 xxxx 2476 HETATM 2477 O HOH S 85 105.364 8.545 80.194 1.00 0.00 xxxx 2477 HETATM 2478 O HOH S 86 76.737 1.253 103.989 1.00 0.00 xxxx 2478 HETATM 2479 O HOH S 87 53.290 10.371 100.636 1.00 0.00 xxxx 2479 HETATM 2480 O HOH S 88 102.105 −8.780 86.538 1.00 0.00 xxxx 2480 HETATM 2481 O HOH S 89 108.979 2.590 87.807 1.00 0.00 xxxx 2481 HETATM 2482 O HOH S 90 101.811 −4.625 66.928 1.00 0.00 xxxx 2482 HETATM 2483 O HOH S 91 86.952 −8.105 61.791 1.00 0.00 xxxx 2483 HETATM 2484 O HOH S 92 75.709 −11.553 83.231 1.00 0.00 xxxx 2484 HETATM 2485 O HOH S 93 69.623 1.107 105.573 1.00 0.00 xxxx 2485 HETATM 2486 O HOH S 94 56.876 15.613 94.651 1.00 0.00 xxxx 2486 HETATM 2487 O HOH S 95 77.223 −1.392 104.142 1.00 0.00 xxxx 2487 HETATM 2488 O HOH S 96 68.977 14.567 81.003 1.00 0.00 xxxx 2488 HETATM 2489 O HOH S 97 103.530 8.231 87.832 1.00 0.00 xxxx 2489 HETATM 2490 O HOH S 98 53.398 16.767 91.322 1.00 0.00 xxxx 2490 HETATM 2491 O HOH S 99 66.904 10.170 74.460 1.00 0.00 xxxx 2491 HETATM 2492 O HOH S 100 66.427 6.432 109.335 1.00 0.00 xxxx 2492 HETATM 2493 O HOH S 101 51.878 17.923 84.653 1.00 0.00 xxxx 2493 HETATM 2494 O HOH S 102 69.516 −7.765 98.830 1.00 0.00 xxxx 2494 HETATM 2495 O HOH S 103 71.156 −6.045 97.297 1.00 0.00 xxxx 2495 HETATM 2496 O HOH S 104 92.484 1.110 96.863 1.00 0.00 xxxx 2496 HETATM 2497 O HOH S 105 104.523 −7.523 86.656 1.00 0.00 xxxx 2497 HETATM 2498 O HOH S 106 53.427 0.356 94.420 1.00 0.00 xxxx 2498 HETATM 2499 O HOH S 107 92.617 −5.406 61.831 1.00 0.00 xxxx 2499 HETATM 2500 O HOH S 108 54.889 −4.851 79.692 1.00 0.00 xxxx 2500 HETATM 2501 O HOH S 109 100.399 −5.002 64.314 1.00 0.00 xxxx 2501 HETATM 2502 O HOH S 110 66.574 15.836 85.863 1.00 0.00 xxxx 2502 HETATM 2503 O HOH S 111 89.301 −16.735 85.704 1.00 0.00 xxxx 2503 HETATM 2504 O HOH S 112 76.257 −2.694 101.852 1.00 0.00 xxxx 2504 HETATM 2505 O HOH S 113 76.407 13.842 79.480 1.00 0.00 xxxx 2505 HETATM 2506 O HOH S 114 77.812 −8.591 71.367 1.00 0.00 xxxx 2506 HETATM 2507 O HOH S 115 62.041 10.695 106.347 1.00 0.00 xxxx 2507 HETATM 2508 O HOH S 116 87.607 2.895 60.722 1.00 0.00 xxxx 2508 HETATM 2509 O HOH S 117 51.846 −1.707 79.894 1.00 0.00 xxxx 2509 HETATM 2510 O HOH S 118 96.615 13.271 68.468 1.00 0.00 xxxx 2510 HETATM 2511 O HOH S 119 68.883 −4.447 104.456 1.00 0.00 xxxx 2511 HETATM 2512 O HOH S 120 78.507 14.813 89.197 1.00 0.00 xxxx 2512 HETATM 2513 O HOH S 121 53.335 12.886 98.107 1.00 0.00 xxxx 2513 HETATM 2514 O HOH S 122 56.296 −5.318 85.105 1.00 0.00 xxxx 2514 HETATM 2515 O HOH S 123 88.573 −1.610 98.089 1.00 0.00 xxxx 2515 HETATM 2516 O HOH S 124 106.958 2.835 68.585 1.00 0.00 xxxx 2516 HETATM 2517 O HOH S 125 91.128 −0.551 95.036 1.00 0.00 xxxx 2517 HETATM 2518 O HOH S 126 87.174 11.082 80.269 1.00 0.00 xxxx 2518 HETATM 2519 O HOH S 127 68.707 10.512 72.620 1.00 0.00 xxxx 2519 HETATM 2520 O HOH S 128 98.671 −0.829 64.980 1.00 0.00 xxxx 2520 HETATM 2521 O HOH S 129 65.315 15.486 79.330 1.00 0.00 xxxx 2521 HETATM 2522 O HOH S 130 80.811 −3.719 67.559 1.00 0.00 xxxx 2522 HETATM 2523 O HOH S 131 90.555 10.401 64.329 1.00 0.00 xxxx 2523 HETATM 2524 O HOH S 132 103.855 1.624 92.996 1.00 0.00 xxxx 2524 HETATM 2525 O HOH S 133 83.476 −11.583 89.782 1.00 0.00 xxxx 2525 HETATM 2526 O HOH S 134 64.555 −6.773 98.920 1.00 0.00 xxxx 2526 HETATM 2527 O HOH S 135 92.827 13.344 66.990 1.00 0.00 xxxx 2527 HETATM 2528 O HOH S 136 79.777 10.104 78.338 1.00 0.00 xxxx 2528 HETATM 2529 O HOH S 137 111.897 −1.398 79.647 1.00 0.00 xxxx 2529 HETATM 2530 O HOH S 138 71.797 16.681 93.656 1.00 0.00 xxxx 2530 HETATM 2531 O HOH S 139 85.233 −15.957 83.898 1.00 0.00 xxxx 2531 HETATM 2532 O HOH S 140 65.068 −1.301 77.154 1.00 0.00 xxxx 2532 HETATM 2533 O HOH S 141 97.222 −19.132 71.009 1.00 0.00 xxxx 2533 HETATM 2534 O HOH S 142 78.384 −12.495 76.563 1.00 0.00 xxxx 2534 HETATM 2535 O HOH S 143 86.982 8.225 70.003 1.00 0.00 xxxx 2535 HETATM 2536 O HOH S 144 95.144 19.750 70.827 1.00 0.00 xxxx 2536 HETATM 2537 O HOH S 145 53.003 4.985 80.845 1.00 0.00 xxxx 2537 HETATM 2538 O HOH S 146 59.733 3.617 106.080 1.00 0.00 xxxx 2538 HETATM 2539 O HOH S 147 55.600 4.084 79.973 1.00 0.00 xxxx 2539 HETATM 2540 O HOH S 148 70.047 13.700 84.283 1.00 0.00 xxxx 2540 HETATM 2541 O HOH S 149 64.010 −3.472 96.174 1.00 0.00 xxxx 2541 HETATM 2542 O HOH S 150 76.709 15.830 97.974 1.00 0.00 xxxx 2542 HETATM 2543 O HOH S 151 87.946 12.867 72.908 1.00 0.00 xxxx 2543 HETATM 2544 O HOH S 152 77.629 11.855 77.995 1.00 0.00 xxxx 2544 HETATM 2545 O HOH S 153 81.571 −9.261 90.403 1.00 0.00 xxxx 2545 HETATM 2546 O HOH S 154 86.206 −15.823 79.020 1.00 0.00 xxxx 2546 HETATM 2547 O HOH S 155 59.732 1.153 76.797 1.00 0.00 xxxx 2547 HETATM 2548 O HOH S 156 62.121 −2.955 94.978 1.00 0.00 xxxx 2548 HETATM 2549 O HOH S 157 89.746 −21.133 79.527 1.00 0.00 xxxx 2549 HETATM 2550 O HOH S 158 50.330 17.743 88.856 1.00 0.00 xxxx 2550 HETATM 2551 O HOH S 159 112.731 −8.840 80.143 1.00 0.00 xxxx 2551 HETATM 2552 O HOH S 160 77.512 −0.547 70.389 1.00 0.00 xxxx 2552 HETATM 2553 O HOH S 161 107.467 −0.669 90.868 1.00 0.00 xxxx 2553 HETATM 2554 O HOH S 162 80.928 6.192 74.700 1.00 0.00 xxxx 2554 HETATM 2555 O HOH S 163 101.626 13.065 71.737 1.00 0.00 xxxx 2555 HETATM 2556 O HOH S 164 66.816 −8.640 98.431 1.00 0.00 xxxx 2556 HETATM 2557 O HOH S 165 52.660 7.548 81.180 1.00 0.00 xxxx 2557 HETATM 2558 O HOH S 166 97.162 12.117 78.436 1.00 0.00 xxxx 2558 HETATM 2559 O HOH S 167 100.084 13.362 78.661 1.00 0.00 xxxx 2559 HETATM 2560 O HOH S 168 112.469 3.315 71.207 1.00 0.00 xxxx 2560 HETATM 2561 O HOH S 169 108.102 0.594 88.724 1.00 0.00 xxxx 2561 HETATM 2562 O HOH S 170 83.349 1.004 67.252 1.00 0.00 xxxx 2562 HETATM 2563 O HOH S 171 82.593 1.925 100.618 1.00 0.00 xxxx 2563 HETATM 2564 O HOH S 172 48.628 5.314 90.692 1.00 0.00 xxxx 2564 HETATM 2565 O HOH S 173 61.875 −5.472 104.466 1.00 0.00 xxxx 2565 HETATM 2566 O HOH S 174 100.676 −10.021 88.842 1.00 0.00 xxxx 2566 HETATM 2567 O HOH S 175 55.519 15.322 78.594 1.00 0.00 xxxx 2567 HETATM 2568 O HOH S 176 86.065 −0.576 97.523 1.00 0.00 xxxx 2568 HETATM 2569 O HOH S 177 97.201 −12.062 59.918 1.00 0.00 xxxx 2569 HETATM 2570 O HOH S 178 47.342 5.542 85.607 1.00 0.00 xxxx 2570 HETATM 2571 O HOH S 179 76.468 −12.251 74.660 1.00 0.00 xxxx 2571 HETATM 2572 O HOH S 180 57.423 18.345 88.406 1.00 0.00 xxxx 2572 HETATM 2573 O HOH S 181 80.597 −2.205 99.237 1.00 0.00 xxxx 2573 HETATM 2574 O HOH S 182 103.774 −12.854 69.894 1.00 0.00 xxxx 2574 HETATM 2575 O HOH S 183 72.156 −11.814 94.679 1.00 0.00 xxxx 2575 HETATM 2576 O HOH S 184 81.554 −13.910 83.030 1.00 0.00 xxxx 2576 HETATM 2577 O HOH S 185 95.027 12.134 77.203 1.00 0.00 xxxx 2577 HETATM 2578 O HOH S 186 68.570 3.287 109.073 1.00 0.00 xxxx 2578 HETATM 2579 O HOH S 187 51.200 7.008 83.661 1.00 0.00 xxxx 2579 HETATM 2580 O HOH S 188 61.837 −9.774 76.675 1.00 0.00 xxxx 2580 HETATM 2581 O HOH S 189 86.757 8.270 84.402 1.00 0.00 xxxx 2581 HETATM 2582 O HOH S 190 49.987 3.480 94.412 1.00 0.00 xxxx 2582 HETATM 2583 O HOH S 191 91.500 2.394 79.859 1.00 0.00 xxxx 2583 HETATM 2584 O HOH S 192 97.145 −21.675 79.236 1.00 0.00 xxxx 2584 HETATM 2585 O HOH S 193 87.618 −4.559 62.051 1.00 0.00 xxxx 2585 HETATM 2586 O HOH S 194 68.160 14.469 86.588 1.00 0.00 xxxx 2586 HETATM 2587 O HOH S 195 66.364 −10.527 74.836 1.00 0.00 xxxx 2587 HETATM 2588 O HOH S 196 74.004 −10.006 96.016 1.00 0.00 xxxx 2588 HETATM 2589 O HOH S 197 82.968 −13.859 87.332 1.00 0.00 xxxx 2589 HETATM 2590 O HOH S 198 108.974 5.718 85.007 1.00 0.00 xxxx 2590 HETATM 2591 O HOH S 199 92.041 7.360 91.914 1.00 0.00 xxxx 2591 HETATM 2592 O HOH S 200 82.751 −1.455 100.240 1.00 0.00 xxxx 2592 HETATM 2593 O HOH S 201 99.141 11.984 83.418 1.00 0.00 xxxx 2593 HETATM 2594 O HOH S 202 49.427 14.666 93.898 1.00 0.00 xxxx 2594 HETATM 2595 O HOH S 203 83.900 −7.265 93.778 1.00 0.00 xxxx 2595 HETATM 2596 O HOH S 204 61.447 5.704 104.520 1.00 0.00 xxxx 2596 HETATM 2597 O HOH S 205 97.789 8.951 91.262 1.00 0.00 xxxx 2597 HETATM 2598 O HOH S 206 87.751 14.201 75.052 1.00 0.00 xxxx 2598 HETATM 2599 O HOH S 207 106.770 8.139 82.289 1.00 0.00 xxxx 2599 HETATM 2600 O HOH S 208 65.822 −10.575 96.934 1.00 0.00 xxxx 2600 HETATM 2601 O HOH S 209 81.050 −5.890 69.224 1.00 0.00 xxxx 2601 HETATM 2602 O HOH S 210 74.647 14.640 86.026 1.00 0.00 xxxx 2602 HETATM 2603 O HOH S 211 108.674 −5.814 74.673 1.00 0.00 xxxx 2603 HETATM 2604 O HOH S 212 77.264 7.891 71.418 1.00 0.00 xxxx 2604 HETATM 2605 O HOH S 213 60.198 −3.619 94.101 1.00 0.00 xxxx 2605 HETATM 2606 O HOH S 214 89.676 −4.554 61.123 1.00 0.00 xxxx 2606 HETATM 2607 O HOH S 215 92.651 −14.696 70.145 1.00 0.00 xxxx 2607 HETATM 2608 O HOH S 216 99.635 9.883 85.489 1.00 0.00 xxxx 2608 HETATM 2609 O HOH S 217 59.538 −4.151 102.501 1.00 0.00 xxxx 2609 HETATM 2610 O HOH S 218 72.310 −20.773 82.100 1.00 0.00 xxxx 2610 HETATM 2611 O HOH S 219 84.674 0.825 92.224 1.00 0.00 xxxx 2611 HETATM 2612 O HOH S 220 104.507 9.632 73.559 1.00 0.00 xxxx 2612 HETATM 2613 O HOH S 221 84.194 1.903 94.312 1.00 0.00 xxxx 2613 HETATM 2614 O HOH S 222 108.610 6.829 81.349 1.00 0.00 xxxx 2614 HETATM 2615 O HOH S 223 98.648 14.172 82.300 1.00 0.00 xxxx 2615 HETATM 2616 O HOH S 224 90.832 12.419 78.701 1.00 0.00 xxxx 2616 HETATM 2617 O HOH S 225 52.540 11.909 76.002 1.00 0.00 xxxx 2617 HETATM 2618 O HOH S 226 105.324 −4.324 67.888 1.00 0.00 xxxx 2618 HETATM 2619 O HOH S 227 79.297 16.150 98.557 1.00 0.00 xxxx 2619 HETATM 2620 O HOH S 228 85.157 −12.672 66.545 1.00 0.00 xxxx 2620 HETATM 2621 O HOH S 229 105.404 −6.081 70.536 1.00 0.00 xxxx 2621 HETATM 2622 O HOH S 230 107.613 −4.792 71.045 1.00 0.00 xxxx 2622 HETATM 2623 O HOH S 231 109.758 3.007 77.248 1.00 0.00 xxxx 2623 HETATM 2624 O HOH S 232 78.855 9.433 98.137 1.00 0.00 xxxx 2624 HETATM 2625 O HOH S 233 77.983 14.271 92.424 1.00 0.00 xxxx 2625 HETATM 2626 O HOH S 234 59.982 −1.213 75.290 1.00 0.00 xxxx 2626 HETATM 2627 O HOH S 235 78.032 −13.631 72.697 1.00 0.00 xxxx 2627 HETATM 2628 O HOH S 236 104.192 −6.382 61.840 1.00 0.00 xxxx 2628 HETATM 2629 O HOH S 237 60.735 10.512 108.811 1.00 0.00 xxxx 2629 HETATM 2630 O HOH S 238 74.989 −1.300 69.668 1.00 0.00 xxxx 2630 HETATM 2631 O HOH S 239 86.035 −17.451 85.940 1.00 0.00 xxxx 2631 HETATM 2632 O HOH S 240 99.535 −10.757 59.554 1.00 0.00 xxxx 2632 HETATM 2633 O HOH S 241 75.396 13.835 83.611 1.00 0.00 xxxx 2633 HETATM 2634 O HOH S 242 90.731 12.998 84.625 1.00 0.00 xxxx 2634 HETATM 2635 O HOH S 243 52.818 14.956 95.847 1.00 0.00 xxxx 2635 HETATM 2636 O HOH S 244 80.322 3.758 85.850 1.00 0.00 xxxx 2636 HETATM 2637 O HOH S 245 55.785 17.408 92.655 1.00 0.00 xxxx 2637 HETATM 2638 O HOH S 246 115.056 3.055 70.761 1.00 0.00 xxxx 2638 HETATM 2639 O HOH S 247 87.204 8.691 79.775 1.00 0.00 xxxx 2639 HETATM 2640 O HOH S 248 67.929 19.944 86.779 1.00 0.00 xxxx 2640 HETATM 2641 O HOH S 249 77.278 −12.670 79.318 1.00 0.00 xxxx 2641 HETATM 2642 O HOH S 250 89.042 −7.911 60.104 1.00 0.00 xxxx 2642 HETATM 2643 O HOH S 251 66.522 19.073 85.218 1.00 0.00 xxxx 2643 HETATM 2644 O HOH S 252 61.727 4.783 107.347 1.00 0.00 xxxx 2644 HETATM 2645 O HOH S 253 106.736 −16.531 79.420 1.00 0.00 xxxx 2645 HETATM 2646 O HOH S 254 73.924 0.038 67.798 1.00 0.00 xxxx 2646 HETATM 2647 O HOH S 255 69.573 20.378 85.052 1.00 0.00 xxxx 2647 HETATM 2648 O HOH S 256 60.911 17.953 97.183 1.00 0.00 xxxx 2648 HETATM 2649 O HOH S 257 64.462 17.633 96.231 1.00 0.00 xxxx 2649 HETATM 2650 O HOH S 258 62.233 18.287 95.393 1.00 0.00 xxxx 2650 HETATM 2651 O HOH S 259 56.704 6.246 102.901 1.00 0.00 xxxx 2651 HETATM 2652 O HOH S 260 100.155 8.120 65.189 1.00 0.00 xxxx 2652 HETATM 2653 O HOH S 261 68.662 4.614 111.034 1.00 0.00 xxxx 2653 HETATM 2654 O HOH S 262 85.282 6.689 68.710 1.00 0.00 xxxx 2654 HETATM 2655 O HOH S 263 53.059 13.136 78.511 1.00 0.00 xxxx 2655 HETATM 2656 O HOH S 264 57.271 −2.144 100.780 1.00 0.00 xxxx 2656 HETATM 2657 O HOH S 265 52.474 −2.587 90.434 1.00 0.00 xxxx 2657 HETATM 2658 O HOH S 266 80.171 6.190 71.814 1.00 0.00 xxxx 2658 HETATM 2659 O HOH S 267 99.575 −11.497 56.975 1.00 0.00 xxxx 2659 HETATM 2660 O HOH S 268 99.589 0.394 99.299 1.00 0.00 xxxx 2660 HETATM 2661 O HOH S 269 69.687 19.479 91.009 1.00 0.00 xxxx 2661 HETATM 2662 O HOH S 270 57.793 0.261 108.756 1.00 0.00 xxxx 2662 HETATM 2663 O HOH S 271 81.987 −13.534 70.405 1.00 0.00 xxxx 2663 HETATM 2664 O HOH S 272 68.352 16.666 93.708 1.00 0.00 xxxx 2664 HETATM 2665 O HOH S 273 52.337 −1.842 99.213 1.00 0.00 xxxx 2665 HETATM 2666 O HOH S 274 113.989 4.886 71.455 1.00 0.00 xxxx 2666 HETATM 2667 O HOH S 275 78.548 −9.578 81.802 1.00 0.00 xxxx 2667 HETATM 2668 O HOH S 276 71.504 −3.457 71.931 1.00 0.00 xxxx 2668 HETATM 2669 O HOH S 277 81.373 −7.989 65.925 1.00 0.00 xxxx 2669 HETATM 2670 O HOH S 278 75.743 2.240 69.380 1.00 0.00 xxxx 2670 HETATM 2671 O HOH S 279 106.824 −16.531 84.712 1.00 0.00 xxxx 2671 HETATM 2672 O HOH S 280 85.750 6.704 62.252 1.00 0.00 xxxx 2672 HETATM 2673 O HOH S 281 85.615 −16.056 74.909 1.00 0.00 xxxx 2673 HETATM 2674 O HOH S 282 54.694 7.097 100.323 1.00 0.00 xxxx 2674 HETATM 2675 O HOH S 283 82.416 −9.126 92.690 1.00 0.00 xxxx 2675 HETATM 2676 O HOH S 284 104.688 −6.624 68.238 1.00 0.00 xxxx 2676 HETATM 2677 O HOH S 285 104.352 6.757 89.424 1.00 0.00 xxxx 2677 HETATM 2678 O HOH S 286 69.910 20.393 88.915 1.00 0.00 xxxx 2678 HETATM 2679 O HOH S 287 61.958 −7.213 97.165 1.00 0.00 xxxx 2679 HETATM 2680 O HOH S 288 94.529 −0.882 102.773 1.00 0.00 xxxx 2680 HETATM 2681 O HOH S 289 77.902 −11.183 83.158 1.00 0.00 xxxx 2681 HETATM 2682 O HOH S 290 107.822 −15.668 77.566 1.00 0.00 xxxx 2682 HETATM 2683 O HOH S 291 95.725 5.302 96.902 1.00 0.00 xxxx 2683 HETATM 2684 O HOH S 292 64.133 3.617 72.467 1.00 0.00 xxxx 2684 HETATM 2685 O HOH S 293 108.451 −6.376 72.578 1.00 0.00 xxxx 2685 HETATM 2686 O HOH S 294 46.400 14.955 93.071 1.00 0.00 xxxx 2686 HETATM 2687 O HOH S 295 58.303 17.796 86.218 1.00 0.00 xxxx 2687 HETATM 2688 O HOH S 296 59.171 18.585 83.785 1.00 0.00 xxxx 2688 HETATM 2689 O HOH S 297 97.679 −18.685 80.897 1.00 0.00 xxxx 2689 HETATM 2690 O HOH S 298 77.741 −14.710 81.359 1.00 0.00 xxxx 2690 HETATM 2691 O HOH S 299 92.006 10.014 61.925 1.00 0.00 xxxx 2691 HETATM 2692 O HOH S 300 61.301 17.558 78.643 1.00 0.00 xxxx 2692 HETATM 2693 O HOH S 301 52.821 0.688 97.645 1.00 0.00 xxxx 2693 HETATM 2694 O HOH S 302 84.779 −15.819 76.983 1.00 0.00 xxxx 2694 HETATM 2695 O HOH S 303 101.048 −19.438 80.682 1.00 0.00 xxxx 2695 HETATM 2696 O HOH S 304 96.756 10.671 86.678 1.00 0.00 xxxx 2696 HETATM 2697 O HOH S 305 52.337 7.315 99.213 1.00 0.00 xxxx 2697 HETATM 2698 O HOH S 306 66.714 −10.256 100.388 1.00 0.00 xxxx 2698 HETATM 2699 O HOH S 307 68.541 17.330 99.380 1.00 0.00 xxxx 2699 HETATM 2700 O HOH S 308 73.679 −7.075 68.628 1.00 0.00 xxxx 2700 HETATM 2701 O HOH S 309 82.946 3.923 67.908 1.00 0.00 xxxx 2701 HETATM 2702 O HOH S 310 87.530 −16.979 69.522 1.00 0.00 xxxx 2702 HETATM 2703 O HOH S 311 90.650 −11.119 59.389 1.00 0.00 xxxx 2703 HETATM 2704 O HOH S 312 102.333 −10.420 90.408 1.00 0.00 xxxx 2704 HETATM 2705 O HOH S 313 76.300 15.569 93.317 1.00 0.00 xxxx 2705 HETATM 2706 O HOH S 314 49.384 −0.292 85.440 1.00 0.00 xxxx 2706 HETATM 2707 O HOH S 315 94.144 −22.571 85.773 1.00 0.00 xxxx 2707 HETATM 2708 O HOH S 316 86.915 −14.572 69.472 1.00 0.00 xxxx 2708 HETATM 2709 O HOH S 317 95.100 0.697 100.381 1.00 0.00 xxxx 2709 HETATM 2710 O HOH S 318 69.328 −3.518 72.553 1.00 0.00 xxxx 2710 HETATM 2711 O HOH S 319 80.753 6.983 69.069 1.00 0.00 xxxx 2711 HETATM 2712 O HOH S 320 46.258 17.814 93.974 1.00 0.00 xxxx 2712 HETATM 2713 O HOH S 321 81.726 −12.988 89.021 1.00 0.00 xxxx 2713 HETATM 2714 O HOH S 322 57.011 −2.865 93.361 1.00 0.00 xxxx 2714 HETATM 2715 O HOH S 323 87.257 7.473 60.108 1.00 0.00 xxxx 2715 HETATM 2716 O HOH S 324 51.673 3.931 78.235 1.00 0.00 xxxx 2716 HETATM 2717 O HOH S 325 100.177 9.710 88.414 1.00 0.00 xxxx 2717

EXAMPLE 11 Crystal Structure Coordinates for a T. thermosaccharolyticum Glucose-Galactose Binding Protein: TTGGBP.17C.BADAN (Badan Attached to F17C Mutant)

Naming is standard three-letter amino acid code.

Atom positions are provided as Cartesian coordinates, using standard Protein Databank (PDB) format. ATOM records refer to amino acid atoms; HETATM records refer to non-amino acid atoms.

Column 1: record type (ATOM or HETATM); column 2: atom number; column 3: atom name (standard naming scheme for amino acids); column 4: residue name (ATOM records), or component name (HETATM records); column 5: chain identifier (A, B, C, . . . ); column 6: amino acid residue sequence number (ATOM records), or component number (HETATM records); columns 7-9: x,y,z atomic Cartesian positional coordinates; column 10: fractional occupancy (set to 1.0 in this listing); column 11: B-factor (ignored in this listing); column 12: file identifier (ignored in this listing); column 13: line number (same as atom number in this listing).

For heteroatom (HETATM) records, the component name (column 4) is as follows:

CA, calcium

HOH, water

BAD, Badan

K, potassium

EDO, ethylene glycol

ATOM 1 N MET A 1 68.218 89.131 176.853 1.00 0.00 xxxx 1 ATOM 2 CA MET A 1 68.822 88.646 175.620 1.00 0.00 xxxx 2 ATOM 3 CB MET A 1 68.234 87.289 175.227 1.00 0.00 xxxx 3 ATOM 4 CG MET A 1 68.484 86.177 176.231 1.00 0.00 xxxx 4 ATOM 5 SD MET A 1 70.237 85.791 176.409 1.00 0.00 xxxx 5 ATOM 6 CE MET A 1 70.690 85.435 174.710 1.00 0.00 xxxx 6 ATOM 7 C MET A 1 68.615 89.642 174.487 1.00 0.00 xxxx 7 ATOM 8 O MET A 1 67.712 90.472 174.536 1.00 0.00 xxxx 8 ATOM 9 N LYS A 2 69.465 89.548 173.473 1.00 0.00 xxxx 9 ATOM 10 CA LYS A 2 69.300 90.303 172.238 1.00 0.00 xxxx 10 ATOM 11 CB LYS A 2 70.554 90.146 171.376 1.00 0.00 xxxx 11 ATOM 12 CG LYS A 2 70.717 91.140 170.251 1.00 0.00 xxxx 12 ATOM 13 CD LYS A 2 72.082 90.940 169.607 1.00 0.00 xxxx 13 ATOM 14 CE LYS A 2 72.374 91.980 168.546 1.00 0.00 xxxx 14 ATOM 15 NZ LYS A 2 73.735 91.788 167.968 1.00 0.00 xxxx 15 ATOM 16 C LYS A 2 68.064 89.811 171.487 1.00 0.00 xxxx 16 ATOM 17 O LYS A 2 67.828 88.604 171.408 1.00 0.00 xxxx 17 ATOM 18 N GLN A 3 67.265 90.725 170.943 1.00 0.00 xxxx 18 ATOM 19 CA GLN A 3 66.123 90.302 170.146 1.00 0.00 xxxx 19 ATOM 20 CB GLN A 3 65.033 91.374 170.089 1.00 0.00 xxxx 20 ATOM 21 CG GLN A 3 63.827 90.924 169.251 1.00 0.00 xxxx 21 ATOM 22 CD GLN A 3 62.685 91.932 169.246 1.00 0.00 xxxx 22 ATOM 23 OE1 GLN A 3 62.731 92.936 168.535 1.00 0.00 xxxx 23 ATOM 24 NE2 GLN A 3 61.652 91.663 170.041 1.00 0.00 xxxx 24 ATOM 25 C GLN A 3 66.591 89.955 168.744 1.00 0.00 xxxx 25 ATOM 26 O GLN A 3 67.319 90.713 168.106 1.00 0.00 xxxx 26 ATOM 27 N LEU A 4 66.192 88.779 168.289 1.00 0.00 xxxx 27 ATOM 28 CA LEU A 4 66.449 88.350 166.930 1.00 0.00 xxxx 28 ATOM 29 CB LEU A 4 67.079 86.957 166.908 1.00 0.00 xxxx 29 ATOM 30 CG LEU A 4 68.443 86.858 167.587 1.00 0.00 xxxx 30 ATOM 31 CD1 LEU A 4 68.891 85.408 167.634 1.00 0.00 xxxx 31 ATOM 32 CD2 LEU A 4 69.469 87.729 166.877 1.00 0.00 xxxx 32 ATOM 33 C LEU A 4 65.126 88.356 166.199 1.00 0.00 xxxx 33 ATOM 34 O LEU A 4 64.123 87.874 166.725 1.00 0.00 xxxx 34 ATOM 35 N ASN A 5 65.123 88.914 164.994 1.00 0.00 xxxx 35 ATOM 36 CA ASN A 5 63.908 89.001 164.199 1.00 0.00 xxxx 36 ATOM 37 CB ASN A 5 63.626 90.440 163.778 1.00 0.00 xxxx 37 ATOM 38 CG ASN A 5 62.959 91.237 164.865 1.00 0.00 xxxx 38 ATOM 39 OD1 ASN A 5 61.748 91.138 165.064 1.00 0.00 xxxx 39 ATOM 40 ND2 ASN A 5 63.739 92.035 165.577 1.00 0.00 xxxx 40 ATOM 41 C ASN A 5 64.027 88.139 162.970 1.00 0.00 xxxx 41 ATOM 42 O ASN A 5 64.981 88.276 162.206 1.00 0.00 xxxx 42 ATOM 43 N ILE A 6 63.056 87.256 162.775 1.00 0.00 xxxx 43 ATOM 44 CA ILE A 6 63.039 86.413 161.588 1.00 0.00 xxxx 44 ATOM 45 CB ILE A 6 63.099 84.931 161.964 1.00 0.00 xxxx 45 ATOM 46 CG1 ILE A 6 64.396 84.647 162.738 1.00 0.00 xxxx 46 ATOM 47 CD1 ILE A 6 64.417 83.296 163.418 1.00 0.00 xxxx 47 ATOM 48 CG2 ILE A 6 62.994 84.065 160.713 1.00 0.00 xxxx 48 ATOM 49 C ILE A 6 61.792 86.731 160.780 1.00 0.00 xxxx 49 ATOM 50 O ILE A 6 60.685 86.727 161.315 1.00 0.00 xxxx 50 ATOM 51 N GLY A 7 61.977 87.040 159.498 1.00 0.00 xxxx 51 ATOM 52 CA GLY A 7 60.844 87.251 158.614 1.00 0.00 xxxx 52 ATOM 53 C GLY A 7 60.351 85.930 158.044 1.00 0.00 xxxx 53 ATOM 54 O GLY A 7 61.110 85.211 157.403 1.00 0.00 xxxx 54 ATOM 55 N VAL A 8 59.086 85.596 158.285 1.00 0.00 xxxx 55 ATOM 56 CA VAL A 8 58.543 84.323 157.803 1.00 0.00 xxxx 56 ATOM 57 CB VAL A 8 58.067 83.416 158.961 1.00 0.00 xxxx 57 ATOM 58 CG1 VAL A 8 57.613 82.063 158.425 1.00 0.00 xxxx 58 ATOM 59 CG2 VAL A 8 59.164 83.248 160.003 1.00 0.00 xxxx 59 ATOM 60 C VAL A 8 57.389 84.593 156.862 1.00 0.00 xxxx 60 ATOM 61 O VAL A 8 56.422 85.258 157.249 1.00 0.00 xxxx 61 ATOM 62 N ALA A 9 57.485 84.095 155.633 1.00 0.00 xxxx 62 ATOM 63 CA ALA A 9 56.372 84.227 154.688 1.00 0.00 xxxx 63 ATOM 64 CB ALA A 9 56.826 84.935 153.410 1.00 0.00 xxxx 64 ATOM 65 C ALA A 9 55.789 82.854 154.364 1.00 0.00 xxxx 65 ATOM 66 O ALA A 9 56.511 81.948 153.948 1.00 0.00 xxxx 66 ATOM 67 N ILE A 10 54.479 82.709 154.583 1.00 0.00 xxxx 67 ATOM 68 CA ILE A 10 53.745 81.456 154.338 1.00 0.00 xxxx 68 ATOM 69 CB ILE A 10 52.776 81.151 155.498 1.00 0.00 xxxx 69 ATOM 70 CG1 ILE A 10 53.533 81.091 156.827 1.00 0.00 xxxx 70 ATOM 71 CD1 ILE A 10 54.530 79.969 156.898 1.00 0.00 xxxx 71 ATOM 72 CG2 ILE A 10 52.018 79.850 155.243 1.00 0.00 xxxx 72 ATOM 73 C ILE A 10 52.993 81.609 153.025 1.00 0.00 xxxx 73 ATOM 74 O ILE A 10 52.393 82.657 152.808 1.00 0.00 xxxx 74 ATOM 75 N TYR A 11 53.007 80.606 152.144 1.00 0.00 xxxx 75 ATOM 76 CA TYR A 11 52.490 80.856 150.790 1.00 0.00 xxxx 76 ATOM 77 CB TYR A 11 52.778 79.669 149.840 1.00 0.00 xxxx 77 ATOM 78 CG TYR A 11 51.675 78.630 149.715 1.00 0.00 xxxx 78 ATOM 79 CD1 TYR A 11 50.763 78.682 148.666 1.00 0.00 xxxx 79 ATOM 80 CE1 TYR A 11 49.747 77.740 148.540 1.00 0.00 xxxx 80 ATOM 81 CZ TYR A 11 49.635 76.725 149.476 1.00 0.00 xxxx 81 ATOM 82 OH TYR A 11 48.625 75.805 149.339 1.00 0.00 xxxx 82 ATOM 83 CE2 TYR A 11 50.532 76.638 150.529 1.00 0.00 xxxx 83 ATOM 84 CD2 TYR A 11 51.556 77.595 150.639 1.00 0.00 xxxx 84 ATOM 85 C TYR A 11 50.993 81.211 150.837 1.00 0.00 xxxx 85 ATOM 86 O TYR A 11 50.560 82.095 150.112 1.00 0.00 xxxx 86 ATOM 87 N LYS A 12 50.229 80.560 151.712 1.00 0.00 xxxx 87 ATOM 88 CA LYS A 12 48.875 81.018 152.025 1.00 0.00 xxxx 88 ATOM 89 CB LYS A 12 47.879 80.636 150.911 1.00 0.00 xxxx 89 ATOM 90 CG LYS A 12 47.377 79.208 150.906 1.00 0.00 xxxx 90 ATOM 91 CD LYS A 12 46.460 78.984 149.692 1.00 0.00 xxxx 91 ATOM 92 CE LYS A 12 45.753 77.645 149.771 1.00 0.00 xxxx 92 ATOM 93 NZ LYS A 12 44.896 77.401 148.570 1.00 0.00 xxxx 93 ATOM 94 C LYS A 12 48.454 80.462 153.383 1.00 0.00 xxxx 94 ATOM 95 O LYS A 12 48.834 79.349 153.753 1.00 0.00 xxxx 95 ATOM 96 N PHE A 13 47.707 81.256 154.148 1.00 0.00 xxxx 96 ATOM 97 CA PHE A 13 47.311 80.834 155.494 1.00 0.00 xxxx 97 ATOM 98 CB PHE A 13 46.861 82.032 156.338 1.00 0.00 xxxx 98 ATOM 99 CG PHE A 13 47.980 82.737 157.069 1.00 0.00 xxxx 99 ATOM 100 CD1 PHE A 13 49.311 82.494 156.765 1.00 0.00 xxxx 100 ATOM 101 CE1 PHE A 13 50.332 83.161 157.445 1.00 0.00 xxxx 101 ATOM 102 CZ PHE A 13 50.021 84.077 158.439 1.00 0.00 xxxx 102 ATOM 103 CE2 PHE A 13 48.697 84.321 158.754 1.00 0.00 xxxx 103 ATOM 104 CD2 PHE A 13 47.687 83.654 158.075 1.00 0.00 xxxx 104 ATOM 105 C PHE A 13 46.197 79.784 155.469 1.00 0.00 xxxx 105 ATOM 106 O PHE A 13 46.102 78.969 156.384 1.00 0.00 xxxx 106 ATOM 107 N ASP A 14 45.364 79.795 154.433 1.00 0.00 xxxx 107 ATOM 108 CA ASP A 14 44.280 78.822 154.342 1.00 0.00 xxxx 108 ATOM 109 CB ASP A 14 43.065 79.419 153.613 1.00 0.00 xxxx 109 ATOM 110 CG ASP A 14 43.364 79.839 152.179 1.00 0.00 xxxx 110 ATOM 111 OD1 ASP A 14 44.501 80.270 151.888 1.00 0.00 xxxx 111 ATOM 112 OD2 ASP A 14 42.439 79.751 151.338 1.00 0.00 xxxx 112 ATOM 113 C ASP A 14 44.742 77.532 153.659 1.00 0.00 xxxx 113 ATOM 114 O ASP A 14 44.102 77.032 152.731 1.00 0.00 xxxx 114 ATOM 115 N ASP A 15 45.873 77.016 154.128 1.00 0.00 xxxx 115 ATOM 116 CA ASP A 15 46.391 75.711 153.722 1.00 0.00 xxxx 116 ATOM 117 CB ASP A 15 47.749 75.858 153.018 1.00 0.00 xxxx 117 ATOM 118 CG ASP A 15 48.339 74.519 152.567 1.00 0.00 xxxx 118 ATOM 119 OD1 ASP A 15 48.195 74.183 151.376 1.00 0.00 xxxx 119 ATOM 120 OD2 ASP A 15 48.969 73.816 153.391 1.00 0.00 xxxx 120 ATOM 121 C ASP A 15 46.506 74.883 154.999 1.00 0.00 xxxx 121 ATOM 122 O ASP A 15 47.150 75.308 155.957 1.00 0.00 xxxx 122 ATOM 123 N THR A 16 45.874 73.715 155.023 1.00 0.00 xxxx 123 ATOM 124 CA THR A 16 45.811 72.911 156.243 1.00 0.00 xxxx 124 ATOM 125 CB THR A 16 44.916 71.675 156.040 1.00 0.00 xxxx 125 ATOM 126 OG1 THR A 16 43.607 72.109 155.636 1.00 0.00 xxxx 126 ATOM 127 CG2 THR A 16 44.800 70.863 157.334 1.00 0.00 xxxx 127 ATOM 128 C THR A 16 47.191 72.473 156.724 1.00 0.00 xxxx 128 ATOM 129 O THR A 16 47.536 72.673 157.887 1.00 0.00 xxxx 129 ATOM 130 N CYS A 17 47.992 71.894 155.838 1.00 0.00 xxxx 130 ATOM 131 CA CYS A 17 49.347 71.505 156.221 1.00 0.00 xxxx 131 ATOM 132 CB CYS A 17 50.024 70.780 155.054 1.00 0.00 xxxx 132 ATOM 133 SG CYS A 17 51.834 70.624 155.124 1.00 0.00 xxxx 133 ATOM 134 C CYS A 17 50.200 72.693 156.684 1.00 0.00 xxxx 134 ATOM 135 O CYS A 17 50.850 72.624 157.731 1.00 0.00 xxxx 135 ATOM 136 N MET A 18 50.199 73.789 155.933 1.00 0.00 xxxx 136 ATOM 137 CA MET A 18 51.103 74.876 156.280 1.00 0.00 xxxx 137 ATOM 138 CB MET A 18 51.261 75.855 155.112 1.00 0.00 xxxx 138 ATOM 139 CG MET A 18 52.133 75.302 153.980 1.00 0.00 xxxx 139 ATOM 140 SD MET A 18 53.707 74.616 154.560 1.00 0.00 xxxx 140 ATOM 141 CE MET A 18 54.419 76.060 155.321 1.00 0.00 xxxx 141 ATOM 142 C MET A 18 50.645 75.594 157.549 1.00 0.00 xxxx 142 ATOM 143 O MET A 18 51.443 76.258 158.200 1.00 0.00 xxxx 143 ATOM 144 N THR A 19 49.368 75.455 157.906 1.00 0.00 xxxx 144 ATOM 145 CA THR A 19 48.891 75.959 159.200 1.00 0.00 xxxx 145 ATOM 146 CB THR A 19 47.364 75.855 159.317 1.00 0.00 xxxx 146 ATOM 147 OG1 THR A 19 46.762 76.756 158.377 1.00 0.00 xxxx 147 ATOM 148 CG2 THR A 19 46.895 76.207 160.727 1.00 0.00 xxxx 148 ATOM 149 C THR A 19 49.567 75.194 160.331 1.00 0.00 xxxx 149 ATOM 150 O THR A 19 49.973 75.778 161.337 1.00 0.00 xxxx 150 ATOM 151 N GLY A 20 49.704 73.885 160.157 1.00 0.00 xxxx 151 ATOM 152 CA GLY A 20 50.429 73.080 161.118 1.00 0.00 xxxx 152 ATOM 153 C GLY A 20 51.880 73.503 161.211 1.00 0.00 xxxx 153 ATOM 154 O GLY A 20 52.445 73.588 162.298 1.00 0.00 xxxx 154 ATOM 155 N VAL A 21 52.492 73.769 160.062 1.00 0.00 xxxx 155 ATOM 156 CA VAL A 21 53.899 74.148 160.051 1.00 0.00 xxxx 156 ATOM 157 CB VAL A 21 54.473 74.174 158.622 1.00 0.00 xxxx 157 ATOM 158 CG1 VAL A 21 55.881 74.758 158.637 1.00 0.00 xxxx 158 ATOM 159 CG2 VAL A 21 54.492 72.778 158.037 1.00 0.00 xxxx 159 ATOM 160 C VAL A 21 54.084 75.495 160.742 1.00 0.00 xxxx 160 ATOM 161 O VAL A 21 54.950 75.639 161.606 1.00 0.00 xxxx 161 ATOM 162 N ARG A 22 53.277 76.492 160.401 1.00 0.00 xxxx 162 ATOM 163 CA ARG A 22 53.521 77.790 161.025 1.00 0.00 xxxx 163 ATOM 164 CB ARG A 22 52.779 78.906 160.292 1.00 0.00 xxxx 164 ATOM 165 CG ARG A 22 51.295 78.771 160.203 1.00 0.00 xxxx 165 ATOM 166 CD ARG A 22 50.786 79.812 159.223 1.00 0.00 xxxx 166 ATOM 167 NE ARG A 22 49.387 79.609 158.882 1.00 0.00 xxxx 167 ATOM 168 CZ ARG A 22 48.385 80.204 159.512 1.00 0.00 xxxx 168 ATOM 169 NH1 ARG A 22 48.638 81.038 160.511 1.00 0.00 xxxx 169 ATOM 170 NH2 ARG A 22 47.135 79.968 159.144 1.00 0.00 xxxx 170 ATOM 171 C ARG A 22 53.182 77.798 162.525 1.00 0.00 xxxx 171 ATOM 172 O ARG A 22 53.855 78.479 163.294 1.00 0.00 xxxx 172 ATOM 173 N ASN A 23 52.185 77.027 162.960 1.00 0.00 xxxx 173 ATOM 174 CA ASN A 23 51.922 76.894 164.395 1.00 0.00 xxxx 174 ATOM 175 CB ASN A 23 50.650 76.086 164.644 1.00 0.00 xxxx 175 ATOM 176 CG ASN A 23 49.403 76.841 164.242 1.00 0.00 xxxx 176 ATOM 177 OD1 ASN A 23 49.447 78.053 164.024 1.00 0.00 xxxx 177 ATOM 178 ND2 ASN A 23 48.283 76.132 164.141 1.00 0.00 xxxx 178 ATOM 179 C ASN A 23 53.096 76.244 165.119 1.00 0.00 xxxx 179 ATOM 180 O ASN A 23 53.463 76.656 166.221 1.00 0.00 xxxx 180 ATOM 181 N ALA A 24 53.693 75.234 164.496 1.00 0.00 xxxx 181 ATOM 182 CA ALA A 24 54.832 74.554 165.107 1.00 0.00 xxxx 182 ATOM 183 CB ALA A 24 55.132 73.256 164.378 1.00 0.00 xxxx 183 ATOM 184 C ALA A 24 56.060 75.467 165.123 1.00 0.00 xxxx 184 ATOM 185 O ALA A 24 56.841 75.441 166.077 1.00 0.00 xxxx 185 ATOM 186 N MET A 25 56.231 76.266 164.073 1.00 0.00 xxxx 186 ATOM 187 CA MET A 25 57.317 77.247 164.038 1.00 0.00 xxxx 187 ATOM 188 CB MET A 25 57.376 77.945 162.680 1.00 0.00 xxxx 188 ATOM 189 CG MET A 25 57.910 77.046 161.580 1.00 0.00 xxxx 189 ATOM 190 SD MET A 25 58.065 77.901 160.004 1.00 0.00 xxxx 190 ATOM 191 CE MET A 25 59.335 79.085 160.417 1.00 0.00 xxxx 191 ATOM 192 C MET A 25 57.157 78.270 165.152 1.00 0.00 xxxx 192 ATOM 193 O MET A 25 58.121 78.614 165.837 1.00 0.00 xxxx 193 ATOM 194 N THR A 26 55.933 78.746 165.333 1.00 0.00 xxxx 194 ATOM 195 CA THR A 26 55.656 79.711 166.388 1.00 0.00 xxxx 195 ATOM 196 CB THR A 26 54.196 80.194 166.321 1.00 0.00 xxxx 196 ATOM 197 OG1 THR A 26 53.990 80.881 165.080 1.00 0.00 xxxx 197 ATOM 198 CG2 THR A 26 53.895 81.138 167.480 1.00 0.00 xxxx 198 ATOM 199 C THR A 26 55.966 79.100 167.758 1.00 0.00 xxxx 199 ATOM 200 O THR A 26 56.518 79.775 168.636 1.00 0.00 xxxx 200 ATOM 201 N ALA A 27 55.660 77.814 167.930 1.00 0.00 xxxx 201 ATOM 202 CA ALA A 27 55.944 77.135 169.194 1.00 0.00 xxxx 202 ATOM 203 CB ALA A 27 55.284 75.757 169.219 1.00 0.00 xxxx 203 ATOM 204 C ALA A 27 57.451 77.008 169.440 1.00 0.00 xxxx 204 ATOM 205 O ALA A 27 57.929 77.222 170.555 1.00 0.00 xxxx 205 ATOM 206 N GLU A 28 58.198 76.661 168.396 1.00 0.00 xxxx 206 ATOM 207 CA GLU A 28 59.646 76.522 168.525 1.00 0.00 xxxx 207 ATOM 208 CB GLU A 28 60.236 75.939 167.244 1.00 0.00 xxxx 208 ATOM 209 CG GLU A 28 59.853 74.496 166.998 1.00 0.00 xxxx 209 ATOM 210 CD GLU A 28 60.289 73.586 168.133 1.00 0.00 xxxx 210 ATOM 211 OE1 GLU A 28 61.391 73.800 168.691 1.00 0.00 xxxx 211 ATOM 212 OE2 GLU A 28 59.520 72.662 168.472 1.00 0.00 xxxx 212 ATOM 213 C GLU A 28 60.334 77.847 168.846 1.00 0.00 xxxx 213 ATOM 214 O GLU A 28 61.358 77.871 169.533 1.00 0.00 xxxx 214 ATOM 215 N ALA A 29 59.765 78.941 168.347 1.00 0.00 xxxx 215 ATOM 216 CA ALA A 29 60.377 80.260 168.470 1.00 0.00 xxxx 216 ATOM 217 CB ALA A 29 59.882 81.168 167.363 1.00 0.00 xxxx 217 ATOM 218 C ALA A 29 60.122 80.920 169.818 1.00 0.00 xxxx 218 ATOM 219 O ALA A 29 60.847 81.841 170.197 1.00 0.00 xxxx 219 ATOM 220 N GLN A 30 59.088 80.469 170.527 1.00 0.00 xxxx 220 ATOM 221 C GLN A 30 59.944 81.122 172.747 1.00 0.00 xxxx 221 ATOM 222 O GLN A 30 60.601 80.114 173.019 1.00 0.00 xxxx 222 ATOM 223 CA GLN A 30 58.724 80.991 171.843 1.00 0.00 xxxx 223 ATOM 224 CB GLN A 30 57.685 80.064 172.494 1.00 0.00 xxxx 224 ATOM 225 CG GLN A 30 57.220 80.480 173.885 1.00 0.00 xxxx 225 ATOM 226 CD GLN A 30 56.502 79.356 174.622 1.00 0.00 xxxx 226 ATOM 227 OE1 GLN A 30 57.126 78.385 175.055 1.00 0.00 xxxx 227 ATOM 228 NE2 GLN A 30 55.186 79.483 174.768 1.00 0.00 xxxx 228 ATOM 229 N GLY A 31 60.247 82.330 173.213 1.00 0.00 xxxx 229 ATOM 230 CA GLY A 31 61.366 82.552 174.111 1.00 0.00 xxxx 230 ATOM 231 C GLY A 31 62.735 82.629 173.456 1.00 0.00 xxxx 231 ATOM 232 O GLY A 31 63.740 82.816 174.142 1.00 0.00 xxxx 232 ATOM 233 N LYS A 32 62.784 82.500 172.134 1.00 0.00 xxxx 233 ATOM 234 CA LYS A 32 64.065 82.426 171.430 1.00 0.00 xxxx 234 ATOM 235 CB LYS A 32 64.214 81.071 170.728 1.00 0.00 xxxx 235 ATOM 236 CG LYS A 32 64.340 79.880 171.664 1.00 0.00 xxxx 236 ATOM 237 CD LYS A 32 64.685 78.617 170.878 1.00 0.00 xxxx 237 ATOM 238 CE LYS A 32 64.614 77.382 171.758 1.00 0.00 xxxx 238 ATOM 239 NZ LYS A 32 63.207 77.104 172.173 1.00 0.00 xxxx 239 ATOM 240 C LYS A 32 64.248 83.539 170.403 1.00 0.00 xxxx 240 ATOM 241 O LYS A 32 65.297 84.184 170.351 1.00 0.00 xxxx 241 ATOM 242 N ALA A 33 63.233 83.742 169.573 1.00 0.00 xxxx 242 ATOM 243 CA ALA A 33 63.301 84.738 168.511 1.00 0.00 xxxx 243 ATOM 244 CB ALA A 33 63.997 84.168 167.288 1.00 0.00 xxxx 244 ATOM 245 C ALA A 33 61.908 85.222 168.148 1.00 0.00 xxxx 245 ATOM 246 O ALA A 33 60.927 84.505 168.321 1.00 0.00 xxxx 246 ATOM 247 N LYS A 34 61.829 86.448 167.648 1.00 0.00 xxxx 247 ATOM 248 CA LYS A 34 60.563 87.009 167.217 1.00 0.00 xxxx 248 ATOM 249 CB LYS A 34 60.564 88.530 167.390 1.00 0.00 xxxx 249 ATOM 250 CG LYS A 34 59.308 89.220 166.878 1.00 0.00 xxxx 250 ATOM 251 CD LYS A 34 59.300 90.688 167.274 1.00 0.00 xxxx 251 ATOM 252 CE LYS A 34 58.087 91.411 166.704 1.00 0.00 xxxx 252 ATOM 253 NZ LYS A 34 58.078 92.851 167.064 1.00 0.00 xxxx 253 ATOM 254 C LYS A 34 60.309 86.641 165.765 1.00 0.00 xxxx 254 ATOM 255 O LYS A 34 61.115 86.966 164.889 1.00 0.00 xxxx 255 ATOM 256 N LEU A 35 59.210 85.933 165.513 1.00 0.00 xxxx 256 ATOM 257 CA LEU A 35 58.799 85.667 164.139 1.00 0.00 xxxx 257 ATOM 258 CB LEU A 35 58.088 84.320 164.016 1.00 0.00 xxxx 258 ATOM 259 CG LEU A 35 58.834 83.075 164.493 1.00 0.00 xxxx 259 ATOM 260 CD1 LEU A 35 58.058 81.826 164.102 1.00 0.00 xxxx 260 ATOM 261 CD2 LEU A 35 60.256 83.025 163.946 1.00 0.00 xxxx 261 ATOM 262 C LEU A 35 57.883 86.779 163.660 1.00 0.00 xxxx 262 ATOM 263 O LEU A 35 56.903 87.131 164.328 1.00 0.00 xxxx 263 ATOM 264 N ASN A 36 58.214 87.342 162.508 1.00 0.00 xxxx 264 ATOM 265 CA ASN A 36 57.350 88.298 161.851 1.00 0.00 xxxx 265 ATOM 266 CB ASN A 36 58.146 89.516 161.395 1.00 0.00 xxxx 266 ATOM 267 CG ASN A 36 58.825 90.224 162.557 1.00 0.00 xxxx 267 ATOM 268 OD1 ASN A 36 58.214 91.050 163.229 1.00 0.00 xxxx 268 ATOM 269 ND2 ASN A 36 60.083 89.879 162.812 1.00 0.00 xxxx 269 ATOM 270 C ASN A 36 56.696 87.561 160.692 1.00 0.00 xxxx 270 ATOM 271 O ASN A 36 57.265 87.452 159.612 1.00 0.00 xxxx 271 ATOM 272 N MET A 37 55.507 87.023 160.943 1.00 0.00 xxxx 272 ATOM 273 CA MET A 37 54.933 86.040 160.028 1.00 0.00 xxxx 273 ATOM 274 CB MET A 37 54.441 84.820 160.796 1.00 0.00 xxxx 274 ATOM 275 CG MET A 37 54.241 83.606 159.905 1.00 0.00 xxxx 275 ATOM 276 SD MET A 37 53.741 82.201 160.891 1.00 0.00 xxxx 276 ATOM 277 CE MET A 37 55.317 81.666 161.542 1.00 0.00 xxxx 277 ATOM 278 C MET A 37 53.804 86.631 159.210 1.00 0.00 xxxx 278 ATOM 279 O MET A 37 52.875 87.236 159.754 1.00 0.00 xxxx 279 ATOM 280 N VAL A 38 53.891 86.443 157.900 1.00 0.00 xxxx 280 ATOM 281 CA VAL A 38 52.949 87.050 156.969 1.00 0.00 xxxx 281 ATOM 282 CB VAL A 38 53.619 88.173 156.151 1.00 0.00 xxxx 282 ATOM 283 CG1 VAL A 38 54.158 89.253 157.081 1.00 0.00 xxxx 283 ATOM 284 CG2 VAL A 38 54.728 87.611 155.267 1.00 0.00 xxxx 284 ATOM 285 C VAL A 38 52.346 86.011 156.038 1.00 0.00 xxxx 285 ATOM 286 O VAL A 38 52.937 84.963 155.770 1.00 0.00 xxxx 286 ATOM 287 N ASP A 39 51.157 86.340 155.550 1.00 0.00 xxxx 287 ATOM 288 CA ASP A 39 50.355 85.500 154.667 1.00 0.00 xxxx 288 ATOM 289 CB ASP A 39 48.890 85.561 155.133 1.00 0.00 xxxx 289 ATOM 290 CG ASP A 39 47.925 84.752 154.270 1.00 0.00 xxxx 290 ATOM 291 OD1 ASP A 39 48.357 84.004 153.366 1.00 0.00 xxxx 291 ATOM 292 OD2 ASP A 39 46.700 84.868 154.522 1.00 0.00 xxxx 292 ATOM 293 C ASP A 39 50.516 86.011 153.238 1.00 0.00 xxxx 293 ATOM 294 O ASP A 39 50.115 87.138 152.935 1.00 0.00 xxxx 294 ATOM 295 N SER A 40 51.092 85.197 152.362 1.00 0.00 xxxx 295 ATOM 296 CA SER A 40 51.324 85.649 150.988 1.00 0.00 xxxx 296 ATOM 297 CB SER A 40 52.541 84.930 150.390 1.00 0.00 xxxx 297 ATOM 298 OG SER A 40 53.719 85.267 151.122 1.00 0.00 xxxx 298 ATOM 299 C SER A 40 50.087 85.467 150.102 1.00 0.00 xxxx 299 ATOM 300 O SER A 40 50.092 85.867 148.938 1.00 0.00 xxxx 300 ATOM 301 N GLN A 41 49.018 84.901 150.661 1.00 0.00 xxxx 301 ATOM 302 CA GLN A 41 47.725 84.784 149.963 1.00 0.00 xxxx 302 ATOM 303 CB GLN A 41 47.038 86.155 149.887 1.00 0.00 xxxx 303 ATOM 304 CG GLN A 41 46.765 86.792 151.256 1.00 0.00 xxxx 304 ATOM 305 CD GLN A 41 45.986 88.102 151.146 1.00 0.00 xxxx 305 ATOM 306 OE1 GLN A 41 46.553 89.182 151.285 1.00 0.00 xxxx 306 ATOM 307 NE2 GLN A 41 44.684 88.004 150.891 1.00 0.00 xxxx 307 ATOM 308 C GLN A 41 47.842 84.186 148.553 1.00 0.00 xxxx 308 ATOM 309 O GLN A 41 47.128 84.599 147.624 1.00 0.00 xxxx 309 ATOM 310 N ASN A 42 48.747 83.218 148.412 1.00 0.00 xxxx 310 ATOM 311 CA ASN A 42 48.961 82.480 147.165 1.00 0.00 xxxx 311 ATOM 312 CB ASN A 42 47.737 81.614 146.848 1.00 0.00 xxxx 312 ATOM 313 CG ASN A 42 48.036 80.518 145.852 1.00 0.00 xxxx 313 ATOM 314 OD1 ASN A 42 49.133 79.957 145.819 1.00 0.00 xxxx 314 ATOM 315 ND2 ASN A 42 47.053 80.213 145.015 1.00 0.00 xxxx 315 ATOM 316 C ASN A 42 49.282 83.417 146.002 1.00 0.00 xxxx 316 ATOM 317 O ASN A 42 48.898 83.167 144.855 1.00 0.00 xxxx 317 ATOM 318 N SER A 43 49.993 84.498 146.311 1.00 0.00 xxxx 318 ATOM 319 CA SER A 43 50.388 85.490 145.320 1.00 0.00 xxxx 319 ATOM 320 CB SER A 43 49.588 86.785 145.512 1.00 0.00 xxxx 320 ATOM 321 OG SER A 43 50.124 87.836 144.719 1.00 0.00 xxxx 321 ATOM 322 C SER A 43 51.878 85.789 145.427 1.00 0.00 xxxx 322 ATOM 323 O SER A 43 52.328 86.321 146.445 1.00 0.00 xxxx 323 ATOM 324 N GLN A 44 52.653 85.458 144.399 1.00 0.00 xxxx 324 ATOM 325 CA GLN A 44 54.073 85.793 144.453 1.00 0.00 xxxx 325 ATOM 326 CB GLN A 44 54.850 85.140 143.310 1.00 0.00 xxxx 326 ATOM 327 CG GLN A 44 56.368 85.194 143.524 1.00 0.00 xxxx 327 ATOM 328 CD GLN A 44 56.808 84.502 144.807 1.00 0.00 xxxx 328 ATOM 329 OE1 GLN A 44 56.407 83.371 145.086 1.00 0.00 xxxx 329 ATOM 330 NE2 GLN A 44 57.639 85.182 145.599 1.00 0.00 xxxx 330 ATOM 331 C GLN A 44 54.314 87.315 144.446 1.00 0.00 xxxx 331 ATOM 332 O GLN A 44 55.211 87.782 145.147 1.00 0.00 xxxx 332 ATOM 333 N PRO A 45 53.541 88.087 143.657 1.00 0.00 xxxx 333 ATOM 334 CA PRO A 45 53.746 89.539 143.776 1.00 0.00 xxxx 334 ATOM 335 CB PRO A 45 52.693 90.113 142.824 1.00 0.00 xxxx 335 ATOM 336 CG PRO A 45 52.587 89.055 141.760 1.00 0.00 xxxx 336 ATOM 337 CD PRO A 45 52.642 87.762 142.526 1.00 0.00 xxxx 337 ATOM 338 C PRO A 45 53.549 90.045 145.204 1.00 0.00 xxxx 338 ATOM 339 O PRO A 45 54.320 90.882 145.667 1.00 0.00 xxxx 339 ATOM 340 N THR A 46 52.555 89.511 145.903 1.00 0.00 xxxx 340 ATOM 341 CA THR A 46 52.363 89.856 147.308 1.00 0.00 xxxx 341 ATOM 342 CB THR A 46 51.108 89.171 147.863 1.00 0.00 xxxx 342 ATOM 343 OG1 THR A 46 49.954 89.728 147.216 1.00 0.00 xxxx 343 ATOM 344 CG2 THR A 46 51.004 89.373 149.368 1.00 0.00 xxxx 344 ATOM 345 C THR A 46 53.581 89.474 148.151 1.00 0.00 xxxx 345 ATOM 346 O THR A 46 54.094 90.284 148.941 1.00 0.00 xxxx 346 ATOM 347 N GLN A 47 54.057 88.247 147.966 1.00 0.00 xxxx 347 ATOM 348 CA GLN A 47 55.214 87.777 148.706 1.00 0.00 xxxx 348 ATOM 349 CB GLN A 47 55.459 86.299 148.425 1.00 0.00 xxxx 349 ATOM 350 CG GLN A 47 56.539 85.727 149.310 1.00 0.00 xxxx 350 ATOM 351 CD GLN A 47 56.655 84.234 149.145 1.00 0.00 xxxx 351 ATOM 352 OE1 GLN A 47 57.354 83.750 148.255 1.00 0.00 xxxx 352 ATOM 353 NE2 GLN A 47 55.963 83.490 149.997 1.00 0.00 xxxx 353 ATOM 354 C GLN A 47 56.472 88.582 148.381 1.00 0.00 xxxx 354 ATOM 355 O GLN A 47 57.287 88.818 149.255 1.00 0.00 xxxx 355 ATOM 356 N ASN A 48 56.625 88.998 147.127 1.00 0.00 xxxx 356 ATOM 357 CA ASN A 48 57.794 89.793 146.754 1.00 0.00 xxxx 357 ATOM 358 CB ASN A 48 57.820 90.061 145.251 1.00 0.00 xxxx 358 ATOM 359 CG ASN A 48 58.164 88.820 144.434 1.00 0.00 xxxx 359 ATOM 360 OD1 ASN A 48 58.698 87.839 144.954 1.00 0.00 xxxx 360 ATOM 361 ND2 ASN A 48 57.881 88.879 143.135 1.00 0.00 xxxx 361 ATOM 362 C ASN A 48 57.802 91.113 147.527 1.00 0.00 xxxx 362 ATOM 363 O ASN A 48 58.854 91.563 147.987 1.00 0.00 xxxx 363 ATOM 364 N ASP A 49 56.626 91.724 147.670 1.00 0.00 xxxx 364 ATOM 365 CA ASP A 49 56.486 92.945 148.462 1.00 0.00 xxxx 365 ATOM 366 CB ASP A 49 55.059 93.504 148.364 1.00 0.00 xxxx 366 ATOM 367 CG ASP A 49 54.752 94.096 147.000 1.00 0.00 xxxx 367 ATOM 368 OD1 ASP A 49 55.700 94.468 146.275 1.00 0.00 xxxx 368 ATOM 369 OD2 ASP A 49 53.555 94.210 146.653 1.00 0.00 xxxx 369 ATOM 370 C ASP A 49 56.833 92.672 149.922 1.00 0.00 xxxx 370 ATOM 371 O ASP A 49 57.471 93.483 150.580 1.00 0.00 xxxx 371 ATOM 372 N GLN A 50 56.416 91.513 150.421 1.00 0.00 xxxx 372 ATOM 373 CA GLN A 50 56.674 91.169 151.817 1.00 0.00 xxxx 373 ATOM 374 CB GLN A 50 55.875 89.922 152.210 1.00 0.00 xxxx 374 ATOM 375 CG GLN A 50 54.378 90.222 152.317 1.00 0.00 xxxx 375 ATOM 376 CD GLN A 50 53.499 88.981 152.264 1.00 0.00 xxxx 376 ATOM 377 OE1 GLN A 50 53.886 87.941 151.732 1.00 0.00 xxxx 377 ATOM 378 NE2 GLN A 50 52.298 89.098 152.816 1.00 0.00 xxxx 378 ATOM 379 C GLN A 50 58.164 90.962 152.055 1.00 0.00 xxxx 379 ATOM 380 O GLN A 50 58.705 91.402 153.067 1.00 0.00 xxxx 380 ATOM 381 N VAL A 51 58.823 90.294 151.112 1.00 0.00 xxxx 381 ATOM 382 CA VAL A 51 60.260 90.081 151.211 1.00 0.00 xxxx 382 ATOM 383 CB VAL A 51 60.764 89.156 150.098 1.00 0.00 xxxx 383 ATOM 384 CG1 VAL A 51 62.308 89.153 150.045 1.00 0.00 xxxx 384 ATOM 385 CG2 VAL A 51 60.231 87.736 150.309 1.00 0.00 xxxx 385 ATOM 386 C VAL A 51 60.984 91.419 151.177 1.00 0.00 xxxx 386 ATOM 387 O VAL A 51 61.912 91.644 151.963 1.00 0.00 xxxx 387 ATOM 388 N ASP A 52 60.562 92.310 150.280 1.00 0.00 xxxx 388 ATOM 389 CA ASP A 52 61.167 93.640 150.219 1.00 0.00 xxxx 389 ATOM 390 CB ASP A 52 60.525 94.504 149.132 1.00 0.00 xxxx 390 ATOM 391 CG ASP A 52 60.923 94.080 147.729 1.00 0.00 xxxx 391 ATOM 392 OD1 ASP A 52 61.889 93.306 147.580 1.00 0.00 xxxx 392 ATOM 393 OD2 ASP A 52 60.268 94.536 146.767 1.00 0.00 xxxx 393 ATOM 394 C ASP A 52 61.056 94.347 151.563 1.00 0.00 xxxx 394 ATOM 395 O ASP A 52 62.012 94.987 152.006 1.00 0.00 xxxx 395 ATOM 396 N LEU A 53 59.905 94.221 152.222 1.00 0.00 xxxx 396 ATOM 397 CA LEU A 53 59.703 94.897 153.504 1.00 0.00 xxxx 397 ATOM 398 CB LEU A 53 58.222 94.893 153.895 1.00 0.00 xxxx 398 ATOM 399 CG LEU A 53 57.869 95.753 155.115 1.00 0.00 xxxx 399 ATOM 400 CD1 LEU A 53 58.301 97.208 154.909 1.00 0.00 xxxx 400 ATOM 401 CD2 LEU A 53 56.381 95.663 155.432 1.00 0.00 xxxx 401 ATOM 402 C LEU A 53 60.547 94.264 154.619 1.00 0.00 xxxx 402 ATOM 403 O LEU A 53 61.093 94.987 155.466 1.00 0.00 xxxx 403 ATOM 404 N PHE A 54 60.636 92.933 154.629 1.00 0.00 xxxx 404 ATOM 405 CA PHE A 54 61.515 92.214 155.560 1.00 0.00 xxxx 405 ATOM 406 CB PHE A 54 61.561 90.708 155.254 1.00 0.00 xxxx 406 ATOM 407 CG PHE A 54 60.346 89.933 155.713 1.00 0.00 xxxx 407 ATOM 408 CD1 PHE A 54 59.575 90.367 156.776 1.00 0.00 xxxx 408 ATOM 409 CE1 PHE A 54 58.461 89.633 157.192 1.00 0.00 xxxx 409 ATOM 410 CZ PHE A 54 58.131 88.452 156.551 1.00 0.00 xxxx 410 ATOM 411 CE2 PHE A 54 58.905 87.998 155.491 1.00 0.00 xxxx 411 ATOM 412 CD2 PHE A 54 60.010 88.737 155.089 1.00 0.00 xxxx 412 ATOM 413 C PHE A 54 62.929 92.783 155.465 1.00 0.00 xxxx 413 ATOM 414 O PHE A 54 63.604 93.023 156.477 1.00 0.00 xxxx 414 ATOM 415 N ILE A 55 63.373 93.007 154.233 1.00 0.00 xxxx 415 ATOM 416 CA ILE A 55 64.732 93.479 153.993 1.00 0.00 xxxx 416 ATOM 417 CB ILE A 55 65.098 93.302 152.511 1.00 0.00 xxxx 417 ATOM 418 CG1 ILE A 55 65.222 91.807 152.197 1.00 0.00 xxxx 418 ATOM 419 CD1 ILE A 55 65.409 91.487 150.726 1.00 0.00 xxxx 419 ATOM 420 CG2 ILE A 55 66.377 94.055 152.177 1.00 0.00 xxxx 420 ATOM 421 C ILE A 55 64.902 94.924 154.457 1.00 0.00 xxxx 421 ATOM 422 O ILE A 55 65.902 95.266 155.093 1.00 0.00 xxxx 422 ATOM 423 N THR A 56 63.916 95.763 154.159 1.00 0.00 xxxx 423 ATOM 424 CA THR A 56 63.933 97.154 154.592 1.00 0.00 xxxx 424 ATOM 425 CB THR A 56 62.713 97.923 154.040 1.00 0.00 xxxx 425 ATOM 426 OG1 THR A 56 62.796 97.967 152.611 1.00 0.00 xxxx 426 ATOM 427 CG2 THR A 56 62.676 99.344 154.581 1.00 0.00 xxxx 427 ATOM 428 C THR A 56 63.951 97.232 156.116 1.00 0.00 xxxx 428 ATOM 429 O THR A 56 64.620 98.091 156.700 1.00 0.00 xxxx 429 ATOM 430 N LYS A 57 63.230 96.315 156.755 1.00 0.00 xxxx 430 ATOM 431 CA LYS A 57 63.159 96.274 158.214 1.00 0.00 xxxx 431 ATOM 432 CB LYS A 57 61.850 95.617 158.655 1.00 0.00 xxxx 432 ATOM 433 CG LYS A 57 60.626 96.490 158.452 1.00 0.00 xxxx 433 ATOM 434 CD LYS A 57 59.376 95.824 159.010 1.00 0.00 xxxx 434 ATOM 435 CE LYS A 57 58.180 96.769 158.976 1.00 0.00 xxxx 435 ATOM 436 NZ LYS A 57 56.935 96.105 159.456 1.00 0.00 xxxx 436 ATOM 437 C LYS A 57 64.344 95.549 158.864 1.00 0.00 xxxx 437 ATOM 438 O LYS A 57 64.375 95.392 160.084 1.00 0.00 xxxx 438 ATOM 439 N LYS A 58 65.309 95.129 158.048 1.00 0.00 xxxx 439 ATOM 440 CA LYS A 58 66.553 94.503 158.516 1.00 0.00 xxxx 440 ATOM 441 CB LYS A 58 67.433 95.534 159.234 1.00 0.00 xxxx 441 ATOM 442 CG LYS A 58 67.875 96.673 158.318 1.00 0.00 xxxx 442 ATOM 443 CD LYS A 58 68.881 97.591 158.989 1.00 0.00 xxxx 443 ATOM 444 CE LYS A 58 69.136 98.827 158.137 1.00 0.00 xxxx 444 ATOM 445 NZ LYS A 58 69.258 98.481 156.688 1.00 0.00 xxxx 445 ATOM 446 C LYS A 58 66.313 93.289 159.416 1.00 0.00 xxxx 446 ATOM 447 O LYS A 58 66.865 93.191 160.516 1.00 0.00 xxxx 447 ATOM 448 N MET A 59 65.483 92.368 158.939 1.00 0.00 xxxx 448 ATOM 449 CA MET A 59 65.349 91.068 159.584 1.00 0.00 xxxx 449 ATOM 450 CB MET A 59 64.430 90.136 158.784 1.00 0.00 xxxx 450 ATOM 451 CG MET A 59 62.963 90.542 158.691 1.00 0.00 xxxx 451 ATOM 452 SD MET A 59 62.059 90.456 160.248 1.00 0.00 xxxx 452 ATOM 453 CE MET A 59 62.015 92.191 160.689 1.00 0.00 xxxx 453 ATOM 454 C MET A 59 66.728 90.444 159.704 1.00 0.00 xxxx 454 ATOM 455 O MET A 59 67.582 90.663 158.846 1.00 0.00 xxxx 455 ATOM 456 N ASN A 60 66.951 89.661 160.756 1.00 0.00 xxxx 456 ATOM 457 CA ASN A 60 68.228 88.965 160.908 1.00 0.00 xxxx 457 ATOM 458 CB ASN A 60 68.446 88.589 162.372 1.00 0.00 xxxx 458 ATOM 459 CG ASN A 60 68.464 89.801 163.279 1.00 0.00 xxxx 459 ATOM 460 OD1 ASN A 60 67.465 90.128 163.918 1.00 0.00 xxxx 460 ATOM 461 ND2 ASN A 60 69.599 90.491 163.318 1.00 0.00 xxxx 461 ATOM 462 C ASN A 60 68.341 87.719 160.026 1.00 0.00 xxxx 462 ATOM 463 O ASN A 60 69.445 87.289 159.692 1.00 0.00 xxxx 463 ATOM 464 N ALA A 61 67.193 87.142 159.669 1.00 0.00 xxxx 464 ATOM 465 CA ALA A 61 67.123 86.004 158.756 1.00 0.00 xxxx 465 ATOM 466 CB ALA A 61 67.477 84.693 159.470 1.00 0.00 xxxx 466 ATOM 467 C ALA A 61 65.727 85.920 158.155 1.00 0.00 xxxx 467 ATOM 468 O ALA A 61 64.780 86.490 158.689 1.00 0.00 xxxx 468 ATOM 469 N LEU A 62 65.616 85.209 157.036 1.00 0.00 xxxx 469 ATOM 470 CA LEU A 62 64.332 84.994 156.379 1.00 0.00 xxxx 470 ATOM 471 CB LEU A 62 64.337 85.542 154.955 1.00 0.00 xxxx 471 ATOM 472 CG LEU A 62 64.779 86.990 154.745 1.00 0.00 xxxx 472 ATOM 473 CD1 LEU A 62 64.760 87.308 153.264 1.00 0.00 xxxx 473 ATOM 474 CD2 LEU A 62 63.876 87.937 155.498 1.00 0.00 xxxx 474 ATOM 475 C LEU A 62 64.027 83.511 156.334 1.00 0.00 xxxx 475 ATOM 476 O LEU A 62 64.923 82.701 156.109 1.00 0.00 xxxx 476 ATOM 477 N ALA A 63 62.762 83.165 156.553 1.00 0.00 xxxx 477 ATOM 478 CA ALA A 63 62.273 81.813 156.314 1.00 0.00 xxxx 478 ATOM 479 CB ALA A 63 61.842 81.136 157.624 1.00 0.00 xxxx 479 ATOM 480 C ALA A 63 61.105 81.935 155.348 1.00 0.00 xxxx 480 ATOM 481 O ALA A 63 60.050 82.455 155.711 1.00 0.00 xxxx 481 ATOM 482 N ILE A 64 61.300 81.468 154.120 1.00 0.00 xxxx 482 ATOM 483 CA ILE A 64 60.337 81.715 153.050 1.00 0.00 xxxx 483 ATOM 484 CB ILE A 64 60.994 82.522 151.905 1.00 0.00 xxxx 484 ATOM 485 CG1 ILE A 64 61.607 83.830 152.432 1.00 0.00 xxxx 485 ATOM 486 CD1 ILE A 64 60.611 84.779 153.082 1.00 0.00 xxxx 486 ATOM 487 CG2 ILE A 64 59.989 82.759 150.772 1.00 0.00 xxxx 487 ATOM 488 C ILE A 64 59.743 80.418 152.501 1.00 0.00 xxxx 488 ATOM 489 O ILE A 64 60.463 79.495 152.140 1.00 0.00 xxxx 489 ATOM 490 N ASN A 65 58.414 80.373 152.463 1.00 0.00 xxxx 490 ATOM 491 CA ASN A 65 57.649 79.299 151.833 1.00 0.00 xxxx 491 ATOM 492 CB ASN A 65 56.519 78.881 152.806 1.00 0.00 xxxx 492 ATOM 493 CG ASN A 65 55.548 77.840 152.252 1.00 0.00 xxxx 493 ATOM 494 OD1 ASN A 65 54.331 78.040 152.335 1.00 0.00 xxxx 494 ATOM 495 ND2 ASN A 65 56.055 76.722 151.762 1.00 0.00 xxxx 495 ATOM 496 C ASN A 65 57.157 79.892 150.497 1.00 0.00 xxxx 496 ATOM 497 O ASN A 65 56.116 80.535 150.451 1.00 0.00 xxxx 497 ATOM 498 N PRO A 66 57.946 79.739 149.413 1.00 0.00 xxxx 498 ATOM 499 CA PRO A 66 57.699 80.580 148.231 1.00 0.00 xxxx 499 ATOM 500 CB PRO A 66 58.934 80.329 147.357 1.00 0.00 xxxx 500 ATOM 501 CG PRO A 66 59.372 78.935 147.731 1.00 0.00 xxxx 501 ATOM 502 CD PRO A 66 59.106 78.847 149.232 1.00 0.00 xxxx 502 ATOM 503 C PRO A 66 56.425 80.206 147.478 1.00 0.00 xxxx 503 ATOM 504 O PRO A 66 56.155 79.020 147.299 1.00 0.00 xxxx 504 ATOM 505 N VAL A 67 55.650 81.199 147.049 1.00 0.00 xxxx 505 ATOM 506 CA VAL A 67 54.412 80.915 146.326 1.00 0.00 xxxx 506 ATOM 507 CB VAL A 67 53.585 82.188 146.099 1.00 0.00 xxxx 507 ATOM 508 CG1 VAL A 67 52.372 81.865 145.252 1.00 0.00 xxxx 508 ATOM 509 CG2 VAL A 67 53.154 82.764 147.427 1.00 0.00 xxxx 509 ATOM 510 C VAL A 67 54.743 80.241 145.004 1.00 0.00 xxxx 510 ATOM 511 O VAL A 67 54.246 79.156 144.698 1.00 0.00 xxxx 511 ATOM 512 N ASP A 68 55.592 80.903 144.226 1.00 0.00 xxxx 512 ATOM 513 CA ASP A 68 56.154 80.356 143.001 1.00 0.00 xxxx 513 ATOM 514 CB ASP A 68 56.103 81.413 141.895 1.00 0.00 xxxx 514 ATOM 515 CG ASP A 68 56.745 80.970 140.598 1.00 0.00 xxxx 515 ATOM 516 OD1 ASP A 68 57.339 79.872 140.524 1.00 0.00 xxxx 516 ATOM 517 OD2 ASP A 68 56.652 81.758 139.624 1.00 0.00 xxxx 517 ATOM 518 C ASP A 68 57.580 79.951 143.345 1.00 0.00 xxxx 518 ATOM 519 O ASP A 68 58.439 80.805 143.546 1.00 0.00 xxxx 519 ATOM 520 N ARG A 69 57.842 78.656 143.450 1.00 0.00 xxxx 520 ATOM 521 CA ARG A 69 59.166 78.263 143.896 1.00 0.00 xxxx 521 ATOM 522 CB ARG A 69 59.214 76.759 144.204 1.00 0.00 xxxx 522 ATOM 523 CG ARG A 69 59.157 75.863 142.992 1.00 0.00 xxxx 523 ATOM 524 CD ARG A 69 58.691 74.465 143.413 1.00 0.00 xxxx 524 ATOM 525 NE ARG A 69 58.616 73.547 142.288 1.00 0.00 xxxx 525 ATOM 526 CZ ARG A 69 59.624 72.786 141.865 1.00 0.00 xxxx 526 ATOM 527 NH1 ARG A 69 60.814 72.830 142.465 1.00 0.00 xxxx 527 ATOM 528 NH2 ARG A 69 59.440 71.977 140.833 1.00 0.00 xxxx 528 ATOM 529 C ARG A 69 60.249 78.666 142.881 1.00 0.00 xxxx 529 ATOM 530 O ARG A 69 61.413 78.803 143.263 1.00 0.00 xxxx 530 ATOM 531 N THR A 70 59.879 78.923 141.625 1.00 0.00 xxxx 531 ATOM 532 CA THR A 70 60.878 79.411 140.661 1.00 0.00 xxxx 532 ATOM 533 CB THR A 70 60.392 79.267 139.184 1.00 0.00 xxxx 533 ATOM 534 OG1 THR A 70 59.329 80.188 138.896 1.00 0.00 xxxx 534 ATOM 535 CG2 THR A 70 59.919 77.842 138.933 1.00 0.00 xxxx 535 ATOM 536 C THR A 70 61.284 80.865 140.955 1.00 0.00 xxxx 536 ATOM 537 O THR A 70 62.320 81.333 140.480 1.00 0.00 xxxx 537 ATOM 538 N ALA A 71 60.510 81.559 141.788 1.00 0.00 xxxx 538 ATOM 539 CA ALA A 71 60.861 82.923 142.190 1.00 0.00 xxxx 539 ATOM 540 CB ALA A 71 59.612 83.672 142.667 1.00 0.00 xxxx 540 ATOM 541 C ALA A 71 61.937 82.971 143.274 1.00 0.00 xxxx 541 ATOM 542 O ALA A 71 62.404 84.052 143.644 1.00 0.00 xxxx 542 ATOM 543 N ALA A 72 62.341 81.808 143.779 1.00 0.00 xxxx 543 ATOM 544 CA ALA A 72 63.334 81.764 144.846 1.00 0.00 xxxx 544 ATOM 545 CB ALA A 72 63.557 80.321 145.328 1.00 0.00 xxxx 545 ATOM 546 C ALA A 72 64.654 82.393 144.397 1.00 0.00 xxxx 546 ATOM 547 O ALA A 72 65.361 82.986 145.207 1.00 0.00 xxxx 547 ATOM 548 N GLY A 73 64.973 82.284 143.106 1.00 0.00 xxxx 548 ATOM 549 CA GLY A 73 66.187 82.877 142.574 1.00 0.00 xxxx 549 ATOM 550 C GLY A 73 66.250 84.379 142.794 1.00 0.00 xxxx 550 ATOM 551 O GLY A 73 67.258 84.908 143.264 1.00 0.00 xxxx 551 ATOM 552 N THR A 74 65.167 85.071 142.457 1.00 0.00 xxxx 552 ATOM 553 CA THR A 74 65.101 86.515 142.667 1.00 0.00 xxxx 553 ATOM 554 CB THR A 74 63.836 87.112 142.007 1.00 0.00 xxxx 554 ATOM 555 OG1 THR A 74 63.900 86.893 140.591 1.00 0.00 xxxx 555 ATOM 556 CG2 THR A 74 63.743 88.608 142.273 1.00 0.00 xxxx 556 ATOM 557 C THR A 74 65.130 86.863 144.158 1.00 0.00 xxxx 557 ATOM 558 O THR A 74 65.742 87.855 144.560 1.00 0.00 xxxx 558 ATOM 559 N ILE A 75 64.492 86.035 144.980 1.00 0.00 xxxx 559 ATOM 560 CA ILE A 75 64.502 86.251 146.423 1.00 0.00 xxxx 560 ATOM 561 CB ILE A 75 63.521 85.295 147.133 1.00 0.00 xxxx 561 ATOM 562 CG1 ILE A 75 62.077 85.609 146.730 1.00 0.00 xxxx 562 ATOM 563 CD1 ILE A 75 61.072 84.586 147.234 1.00 0.00 xxxx 563 ATOM 564 CG2 ILE A 75 63.693 85.377 148.649 1.00 0.00 xxxx 564 ATOM 565 C ILE A 75 65.924 86.099 146.973 1.00 0.00 xxxx 565 ATOM 566 O ILE A 75 66.351 86.874 147.829 1.00 0.00 xxxx 566 ATOM 567 N ILE A 76 66.654 85.101 146.479 1.00 0.00 xxxx 567 ATOM 568 CA ILE A 76 68.037 84.902 146.899 1.00 0.00 xxxx 568 ATOM 569 CB ILE A 76 68.615 83.585 146.343 1.00 0.00 xxxx 569 ATOM 570 CG1 ILE A 76 67.917 82.387 146.999 1.00 0.00 xxxx 570 ATOM 571 CD1 ILE A 76 68.122 81.063 146.273 1.00 0.00 xxxx 571 ATOM 572 CG2 ILE A 76 70.123 83.526 146.570 1.00 0.00 xxxx 572 ATOM 573 C ILE A 76 68.884 86.109 146.491 1.00 0.00 xxxx 573 ATOM 574 O ILE A 76 69.702 86.583 147.280 1.00 0.00 xxxx 574 ATOM 575 N ASP A 77 68.675 86.622 145.276 1.00 0.00 xxxx 575 ATOM 576 CA ASP A 77 69.396 87.818 144.827 1.00 0.00 xxxx 576 ATOM 577 CB ASP A 77 68.917 88.274 143.447 1.00 0.00 xxxx 577 ATOM 578 CG ASP A 77 69.400 87.373 142.329 1.00 0.00 xxxx 578 ATOM 579 OD1 ASP A 77 70.394 86.651 142.530 1.00 0.00 xxxx 579 ATOM 580 OD2 ASP A 77 68.786 87.399 141.241 1.00 0.00 xxxx 580 ATOM 581 C ASP A 77 69.236 88.971 145.812 1.00 0.00 xxxx 581 ATOM 582 O ASP A 77 70.217 89.600 146.202 1.00 0.00 xxxx 582 ATOM 583 N LYS A 78 67.993 89.238 146.206 1.00 0.00 xxxx 583 ATOM 584 CA LYS A 78 67.697 90.340 147.114 1.00 0.00 xxxx 584 ATOM 585 CB LYS A 78 66.187 90.539 147.253 1.00 0.00 xxxx 585 ATOM 586 CG LYS A 78 65.482 91.006 145.993 1.00 0.00 xxxx 586 ATOM 587 CD LYS A 78 63.968 90.934 146.185 1.00 0.00 xxxx 587 ATOM 588 CE LYS A 78 63.205 91.440 144.968 1.00 0.00 xxxx 588 ATOM 589 NZ LYS A 78 63.228 92.922 144.844 1.00 0.00 xxxx 589 ATOM 590 C LYS A 78 68.309 90.094 148.485 1.00 0.00 xxxx 590 ATOM 591 O LYS A 78 68.882 91.000 149.095 1.00 0.00 xxxx 591 ATOM 592 N ALA A 79 68.177 88.864 148.962 1.00 0.00 xxxx 592 ATOM 593 CA ALA A 79 68.713 88.492 150.266 1.00 0.00 xxxx 593 ATOM 594 CB ALA A 79 68.272 87.087 150.631 1.00 0.00 xxxx 594 ATOM 595 C ALA A 79 70.237 88.597 150.290 1.00 0.00 xxxx 595 ATOM 596 O ALA A 79 70.813 89.107 151.251 1.00 0.00 xxxx 596 ATOM 597 N LYS A 80 70.885 88.117 149.231 1.00 0.00 xxxx 597 ATOM 598 CA LYS A 80 72.346 88.192 149.124 1.00 0.00 xxxx 598 ATOM 599 CB LYS A 80 72.829 87.505 147.843 1.00 0.00 xxxx 599 ATOM 600 CG LYS A 80 74.345 87.412 147.695 1.00 0.00 xxxx 600 ATOM 601 CD LYS A 80 74.716 86.576 146.474 1.00 0.00 xxxx 601 ATOM 602 CE LYS A 80 76.222 86.416 146.331 1.00 0.00 xxxx 602 ATOM 603 NZ LYS A 80 76.901 87.724 146.158 1.00 0.00 xxxx 603 ATOM 604 C LYS A 80 72.823 89.638 149.149 1.00 0.00 xxxx 604 ATOM 605 O LYS A 80 73.796 89.968 149.826 1.00 0.00 xxxx 605 ATOM 606 N GLN A 81 72.127 90.497 148.410 1.00 0.00 xxxx 606 ATOM 607 CA GLN A 81 72.466 91.910 148.354 1.00 0.00 xxxx 607 ATOM 608 CB GLN A 81 71.571 92.629 147.344 1.00 0.00 xxxx 608 ATOM 609 CG GLN A 81 71.899 94.102 147.167 1.00 0.00 xxxx 609 ATOM 610 CD GLN A 81 73.342 94.340 146.750 1.00 0.00 xxxx 610 ATOM 611 OE1 GLN A 81 73.913 93.578 145.966 1.00 0.00 xxxx 611 ATOM 612 NE2 GLN A 81 73.940 95.403 147.279 1.00 0.00 xxxx 612 ATOM 613 C GLN A 81 72.344 92.550 149.735 1.00 0.00 xxxx 613 ATOM 614 O GLN A 81 73.172 93.369 150.123 1.00 0.00 xxxx 614 ATOM 615 N ALA A 82 71.326 92.145 150.487 1.00 0.00 xxxx 615 ATOM 616 CA ALA A 82 71.095 92.689 151.823 1.00 0.00 xxxx 616 ATOM 617 CB ALA A 82 69.618 92.589 152.166 1.00 0.00 xxxx 617 ATOM 618 C ALA A 82 71.928 91.984 152.900 1.00 0.00 xxxx 618 ATOM 619 O ALA A 82 71.942 92.409 154.058 1.00 0.00 xxxx 619 ATOM 620 N ASN A 83 72.609 90.911 152.506 1.00 0.00 xxxx 620 ATOM 621 CA ASN A 83 73.337 90.025 153.419 1.00 0.00 xxxx 621 ATOM 622 CB ASN A 83 74.565 90.740 154.004 1.00 0.00 xxxx 622 ATOM 623 CG ASN A 83 75.580 89.772 154.579 1.00 0.00 xxxx 623 ATOM 624 OD1 ASN A 83 75.617 88.597 154.209 1.00 0.00 xxxx 624 ATOM 625 ND2 ASN A 83 76.400 90.256 155.498 1.00 0.00 xxxx 625 ATOM 626 C ASN A 83 72.436 89.487 154.540 1.00 0.00 xxxx 626 ATOM 627 O ASN A 83 72.835 89.408 155.699 1.00 0.00 xxxx 627 ATOM 628 N ILE A 84 71.215 89.108 154.173 1.00 0.00 xxxx 628 ATOM 629 CA ILE A 84 70.283 88.471 155.098 1.00 0.00 xxxx 629 ATOM 630 CB ILE A 84 68.926 89.201 155.137 1.00 0.00 xxxx 630 ATOM 631 CG1 ILE A 84 69.110 90.662 155.557 1.00 0.00 xxxx 631 ATOM 632 CD1 ILE A 84 67.799 91.458 155.568 1.00 0.00 xxxx 632 ATOM 633 CG2 ILE A 84 67.970 88.472 156.085 1.00 0.00 xxxx 633 ATOM 634 C ILE A 84 70.096 87.022 154.673 1.00 0.00 xxxx 634 ATOM 635 O ILE A 84 69.549 86.760 153.605 1.00 0.00 xxxx 635 ATOM 636 N PRO A 85 70.566 86.072 155.494 1.00 0.00 xxxx 636 ATOM 637 CA PRO A 85 70.477 84.653 155.134 1.00 0.00 xxxx 637 ATOM 638 CB PRO A 85 71.146 83.939 156.313 1.00 0.00 xxxx 638 ATOM 639 CG PRO A 85 71.926 84.981 157.018 1.00 0.00 xxxx 639 ATOM 640 CD PRO A 85 71.196 86.272 156.807 1.00 0.00 xxxx 640 ATOM 641 C PRO A 85 69.036 84.200 154.989 1.00 0.00 xxxx 641 ATOM 642 O PRO A 85 68.147 84.804 155.588 1.00 0.00 xxxx 642 ATOM 643 N VAL A 86 68.805 83.152 154.208 1.00 0.00 xxxx 643 ATOM 644 CA VAL A 86 67.445 82.710 153.973 1.00 0.00 xxxx 644 ATOM 645 CB VAL A 86 66.891 83.341 152.664 1.00 0.00 xxxx 645 ATOM 646 CG1 VAL A 86 67.839 83.113 151.486 1.00 0.00 xxxx 646 ATOM 647 CG2 VAL A 86 65.501 82.813 152.349 1.00 0.00 xxxx 647 ATOM 648 C VAL A 86 67.355 81.197 153.939 1.00 0.00 xxxx 648 ATOM 649 O VAL A 86 68.173 80.523 153.316 1.00 0.00 xxxx 649 ATOM 650 N VAL A 87 66.358 80.670 154.637 1.00 0.00 xxxx 650 ATOM 651 CA VAL A 87 66.011 79.268 154.517 1.00 0.00 xxxx 651 ATOM 652 CB VAL A 87 66.050 78.545 155.891 1.00 0.00 xxxx 652 ATOM 653 CG1 VAL A 87 65.197 79.281 156.950 1.00 0.00 xxxx 653 ATOM 654 CG2 VAL A 87 65.647 77.059 155.757 1.00 0.00 xxxx 654 ATOM 655 C VAL A 87 64.642 79.193 153.854 1.00 0.00 xxxx 655 ATOM 656 O VAL A 87 63.702 79.888 154.250 1.00 0.00 xxxx 656 ATOM 657 N PHE A 88 64.545 78.376 152.815 1.00 0.00 xxxx 657 ATOM 658 CA PHE A 88 63.271 78.124 152.168 1.00 0.00 xxxx 658 ATOM 659 CB PHE A 88 63.426 78.003 150.652 1.00 0.00 xxxx 659 ATOM 660 CG PHE A 88 63.847 79.285 149.980 1.00 0.00 xxxx 660 ATOM 661 CD1 PHE A 88 65.194 79.564 149.773 1.00 0.00 xxxx 661 ATOM 662 CE1 PHE A 88 65.594 80.743 149.161 1.00 0.00 xxxx 662 ATOM 663 CZ PHE A 88 64.633 81.661 148.744 1.00 0.00 xxxx 663 ATOM 664 CE2 PHE A 88 63.286 81.391 148.944 1.00 0.00 xxxx 664 ATOM 665 CD2 PHE A 88 62.900 80.209 149.564 1.00 0.00 xxxx 665 ATOM 666 C PHE A 88 62.705 76.841 152.739 1.00 0.00 xxxx 666 ATOM 667 O PHE A 88 63.451 76.004 153.249 1.00 0.00 xxxx 667 ATOM 668 N PHE A 89 61.393 76.672 152.658 1.00 0.00 xxxx 668 ATOM 669 CA PHE A 89 60.818 75.423 153.159 1.00 0.00 xxxx 669 ATOM 670 CB PHE A 89 60.593 75.478 154.697 1.00 0.00 xxxx 670 ATOM 671 CG PHE A 89 59.650 76.566 155.184 1.00 0.00 xxxx 671 ATOM 672 CD1 PHE A 89 60.063 77.896 155.266 1.00 0.00 xxxx 672 ATOM 673 CE1 PHE A 89 59.200 78.894 155.744 1.00 0.00 xxxx 673 ATOM 674 CZ PHE A 89 57.931 78.557 156.176 1.00 0.00 xxxx 674 ATOM 675 CE2 PHE A 89 57.517 77.232 156.118 1.00 0.00 xxxx 675 ATOM 676 CD2 PHE A 89 58.373 76.246 155.627 1.00 0.00 xxxx 676 ATOM 677 C PHE A 89 59.535 75.069 152.426 1.00 0.00 xxxx 677 ATOM 678 O PHE A 89 58.814 75.946 151.946 1.00 0.00 xxxx 678 ATOM 679 N ASN A 90 59.332 73.754 152.289 1.00 0.00 xxxx 679 ATOM 680 CA ASN A 90 58.098 73.099 151.807 1.00 0.00 xxxx 680 ATOM 681 CB ASN A 90 56.883 73.575 152.622 1.00 0.00 xxxx 681 ATOM 682 CG ASN A 90 55.556 73.178 151.972 1.00 0.00 xxxx 682 ATOM 683 OD1 ASN A 90 54.938 73.975 151.266 1.00 0.00 xxxx 683 ATOM 684 ND2 ASN A 90 55.117 71.939 152.207 1.00 0.00 xxxx 684 ATOM 685 C ASN A 90 57.807 73.246 150.302 1.00 0.00 xxxx 685 ATOM 686 O ASN A 90 57.298 72.315 149.681 1.00 0.00 xxxx 686 ATOM 687 N ARG A 91 58.125 74.403 149.724 1.00 0.00 xxxx 687 ATOM 688 CA ARG A 91 58.036 74.592 148.280 1.00 0.00 xxxx 688 ATOM 689 C ARG A 91 59.468 74.816 147.794 1.00 0.00 xxxx 689 ATOM 690 O ARG A 91 60.124 75.773 148.202 1.00 0.00 xxxx 690 ATOM 691 CB ARG A 91 57.087 75.751 147.949 1.00 0.00 xxxx 691 ATOM 692 CG ARG A 91 55.655 75.433 148.407 1.00 0.00 xxxx 692 ATOM 693 CD ARG A 91 54.789 76.659 148.670 1.00 0.00 xxxx 693 ATOM 694 NE ARG A 91 54.151 77.190 147.458 1.00 0.00 xxxx 694 ATOM 695 CZ ARG A 91 53.015 76.739 146.941 1.00 0.00 xxxx 695 ATOM 696 NH1 ARG A 91 52.362 75.719 147.501 1.00 0.00 xxxx 696 ATOM 697 NH2 ARG A 91 52.519 77.309 145.846 1.00 0.00 xxxx 697 ATOM 698 N GLU A 92 59.968 73.890 146.977 1.00 0.00 xxxx 698 ATOM 699 CA GLU A 92 61.422 73.749 146.804 1.00 0.00 xxxx 699 ATOM 700 CB GLU A 92 61.763 72.272 146.560 1.00 0.00 xxxx 700 ATOM 701 CG GLU A 92 63.259 71.978 146.579 1.00 0.00 xxxx 701 ATOM 702 CD GLU A 92 63.581 70.526 146.255 1.00 0.00 xxxx 702 ATOM 703 OE1 GLU A 92 62.669 69.664 146.317 1.00 0.00 xxxx 703 ATOM 704 OE2 GLU A 92 64.758 70.244 145.929 1.00 0.00 xxxx 704 ATOM 705 C GLU A 92 62.045 74.601 145.689 1.00 0.00 xxxx 705 ATOM 706 O GLU A 92 61.686 74.480 144.528 1.00 0.00 xxxx 706 ATOM 707 N PRO A 93 63.012 75.455 146.038 1.00 0.00 xxxx 707 ATOM 708 CA PRO A 93 63.750 76.176 144.988 1.00 0.00 xxxx 708 ATOM 709 CB PRO A 93 64.800 76.963 145.766 1.00 0.00 xxxx 709 ATOM 710 CG PRO A 93 64.178 77.136 147.143 1.00 0.00 xxxx 710 ATOM 711 CD PRO A 93 63.424 75.864 147.392 1.00 0.00 xxxx 711 ATOM 712 C PRO A 93 64.435 75.237 144.017 1.00 0.00 xxxx 712 ATOM 713 O PRO A 93 64.810 74.123 144.393 1.00 0.00 xxxx 713 ATOM 714 N LEU A 94 64.606 75.690 142.781 1.00 0.00 xxxx 714 ATOM 715 CA LEU A 94 65.328 74.912 141.787 1.00 0.00 xxxx 715 ATOM 716 CB LEU A 94 65.233 75.591 140.425 1.00 0.00 xxxx 716 ATOM 717 CG LEU A 94 63.785 75.791 139.968 1.00 0.00 xxxx 717 ATOM 718 CD1 LEU A 94 63.734 76.670 138.728 1.00 0.00 xxxx 718 ATOM 719 CD2 LEU A 94 63.095 74.455 139.709 1.00 0.00 xxxx 719 ATOM 720 C LEU A 94 66.781 74.727 142.223 1.00 0.00 xxxx 720 ATOM 721 O LEU A 94 67.381 75.624 142.813 1.00 0.00 xxxx 721 ATOM 722 N PRO A 95 67.340 73.542 141.956 1.00 0.00 xxxx 722 ATOM 723 CA PRO A 95 68.666 73.193 142.475 1.00 0.00 xxxx 723 ATOM 724 CB PRO A 95 68.930 71.809 141.863 1.00 0.00 xxxx 724 ATOM 725 CG PRO A 95 67.860 71.592 140.834 1.00 0.00 xxxx 725 ATOM 726 CD PRO A 95 66.697 72.411 141.269 1.00 0.00 xxxx 726 ATOM 727 C PRO A 95 69.755 74.205 142.096 1.00 0.00 xxxx 727 ATOM 728 O PRO A 95 70.580 74.519 142.943 1.00 0.00 xxxx 728 ATOM 729 N GLU A 96 69.737 74.741 140.877 1.00 0.00 xxxx 729 ATOM 730 CA GLU A 96 70.756 75.714 140.488 1.00 0.00 xxxx 730 ATOM 731 CB GLU A 96 70.749 75.933 138.974 1.00 0.00 xxxx 731 ATOM 732 CG GLU A 96 71.164 74.707 138.180 1.00 0.00 xxxx 732 ATOM 733 CD GLU A 96 72.488 74.139 138.652 1.00 0.00 xxxx 733 ATOM 734 OE1 GLU A 96 73.461 74.918 138.775 1.00 0.00 xxxx 734 ATOM 735 OE2 GLU A 96 72.550 72.919 138.920 1.00 0.00 xxxx 735 ATOM 736 C GLU A 96 70.574 77.050 141.213 1.00 0.00 xxxx 736 ATOM 737 O GLU A 96 71.546 77.766 141.459 1.00 0.00 xxxx 737 ATOM 738 N ASP A 97 69.336 77.386 141.566 1.00 0.00 xxxx 738 ATOM 739 CA ASP A 97 69.094 78.607 142.328 1.00 0.00 xxxx 739 ATOM 740 CB ASP A 97 67.596 78.919 142.410 1.00 0.00 xxxx 740 ATOM 741 CG ASP A 97 67.067 79.559 141.140 1.00 0.00 xxxx 741 ATOM 742 OD1 ASP A 97 67.891 79.972 140.292 1.00 0.00 xxxx 742 ATOM 743 OD2 ASP A 97 65.832 79.670 141.000 1.00 0.00 xxxx 743 ATOM 744 C ASP A 97 69.694 78.493 143.725 1.00 0.00 xxxx 744 ATOM 745 O ASP A 97 70.181 79.480 144.271 1.00 0.00 xxxx 745 ATOM 746 N MET A 98 69.684 77.279 144.278 1.00 0.00 xxxx 746 ATOM 747 CA MET A 98 70.254 77.018 145.599 1.00 0.00 xxxx 747 ATOM 748 CB MET A 98 69.955 75.577 146.039 1.00 0.00 xxxx 748 ATOM 749 CG MET A 98 68.467 75.284 146.309 1.00 0.00 xxxx 749 ATOM 750 SD MET A 98 67.801 76.201 147.721 1.00 0.00 xxxx 750 ATOM 751 CE MET A 98 68.810 75.553 149.068 1.00 0.00 xxxx 751 ATOM 752 C MET A 98 71.768 77.275 145.614 1.00 0.00 xxxx 752 ATOM 753 O MET A 98 72.340 77.557 146.664 1.00 0.00 xxxx 753 ATOM 754 N LYS A 99 72.410 77.193 144.452 1.00 0.00 xxxx 754 ATOM 755 CA LYS A 99 73.858 77.393 144.374 1.00 0.00 xxxx 755 ATOM 756 CB LYS A 99 74.431 76.572 143.221 1.00 0.00 xxxx 756 ATOM 757 CG LYS A 99 74.265 75.078 143.389 1.00 0.00 xxxx 757 ATOM 758 CD LYS A 99 74.964 74.331 142.266 1.00 0.00 xxxx 758 ATOM 759 CE LYS A 99 74.695 72.840 142.343 1.00 0.00 xxxx 759 ATOM 760 NZ LYS A 99 75.280 72.127 141.177 1.00 0.00 xxxx 760 ATOM 761 C LYS A 99 74.280 78.858 144.211 1.00 0.00 xxxx 761 ATOM 762 O LYS A 99 75.475 79.153 144.093 1.00 0.00 xxxx 762 ATOM 763 N LYS A 100 73.312 79.774 144.212 1.00 0.00 xxxx 763 ATOM 764 CA LYS A 100 73.601 81.195 144.001 1.00 0.00 xxxx 764 ATOM 765 CB LYS A 100 72.302 81.956 143.700 1.00 0.00 xxxx 765 ATOM 766 CG LYS A 100 71.752 81.702 142.304 1.00 0.00 xxxx 766 ATOM 767 CD LYS A 100 70.279 82.067 142.192 1.00 0.00 xxxx 767 ATOM 768 CE LYS A 100 70.069 83.561 142.148 1.00 0.00 xxxx 768 ATOM 769 NZ LYS A 100 70.519 84.144 140.855 1.00 0.00 xxxx 769 ATOM 770 C LYS A 100 74.313 81.856 145.186 1.00 0.00 xxxx 770 ATOM 771 O LYS A 100 74.978 82.878 145.026 1.00 0.00 xxxx 771 ATOM 772 N TRP A 101 74.173 81.273 146.372 1.00 0.00 xxxx 772 ATOM 773 CA TRP A 101 74.705 81.880 147.591 1.00 0.00 xxxx 773 ATOM 774 CB TRP A 101 73.730 82.932 148.125 1.00 0.00 xxxx 774 ATOM 775 CG TRP A 101 74.285 83.873 149.158 1.00 0.00 xxxx 775 ATOM 776 CD1 TRP A 101 75.590 84.247 149.326 1.00 0.00 xxxx 776 ATOM 777 NE1 TRP A 101 75.697 85.135 150.378 1.00 0.00 xxxx 777 ATOM 778 CE2 TRP A 101 74.451 85.343 150.909 1.00 0.00 xxxx 778 ATOM 779 CD2 TRP A 101 73.536 84.567 150.165 1.00 0.00 xxxx 779 ATOM 780 CE3 TRP A 101 72.181 84.603 150.512 1.00 0.00 xxxx 780 ATOM 781 CZ3 TRP A 101 71.785 85.406 151.573 1.00 0.00 xxxx 781 ATOM 782 CH2 TRP A 101 72.716 86.169 152.289 1.00 0.00 xxxx 782 ATOM 783 CZ2 TRP A 101 74.051 86.153 151.975 1.00 0.00 xxxx 783 ATOM 784 C TRP A 101 74.948 80.804 148.638 1.00 0.00 xxxx 784 ATOM 785 O TRP A 101 74.258 79.784 148.642 1.00 0.00 xxxx 785 ATOM 786 N ASP A 102 75.911 81.031 149.529 1.00 0.00 xxxx 786 ATOM 787 CA ASP A 102 76.271 80.015 150.516 1.00 0.00 xxxx 787 ATOM 788 CB ASP A 102 77.797 79.937 150.667 1.00 0.00 xxxx 788 ATOM 789 CG ASP A 102 78.411 81.214 151.221 1.00 0.00 xxxx 789 ATOM 790 OD1 ASP A 102 77.731 82.261 151.270 1.00 0.00 xxxx 790 ATOM 791 OD2 ASP A 102 79.603 81.170 151.607 1.00 0.00 xxxx 791 ATOM 792 C ASP A 102 75.612 80.254 151.872 1.00 0.00 xxxx 792 ATOM 793 O ASP A 102 76.036 79.692 152.882 1.00 0.00 xxxx 793 ATOM 794 N LYS A 103 74.569 81.079 151.888 1.00 0.00 xxxx 794 ATOM 795 CA LYS A 103 73.775 81.274 153.099 1.00 0.00 xxxx 795 ATOM 796 CB LYS A 103 73.948 82.698 153.648 1.00 0.00 xxxx 796 ATOM 797 CG LYS A 103 75.400 83.028 154.036 1.00 0.00 xxxx 797 ATOM 798 CD LYS A 103 75.491 84.301 154.862 1.00 0.00 xxxx 798 ATOM 799 CE LYS A 103 76.930 84.638 155.211 1.00 0.00 xxxx 799 ATOM 800 NZ LYS A 103 77.020 85.940 155.922 1.00 0.00 xxxx 800 ATOM 801 C LYS A 103 72.314 80.970 152.799 1.00 0.00 xxxx 801 ATOM 802 O LYS A 103 71.412 81.586 153.365 1.00 0.00 xxxx 802 ATOM 803 N VAL A 104 72.094 80.004 151.909 1.00 0.00 xxxx 803 ATOM 804 CA VAL A 104 70.753 79.586 151.511 1.00 0.00 xxxx 804 ATOM 805 CB VAL A 104 70.521 79.835 150.010 1.00 0.00 xxxx 805 ATOM 806 CG1 VAL A 104 69.112 79.405 149.604 1.00 0.00 xxxx 806 ATOM 807 CG2 VAL A 104 70.758 81.302 149.682 1.00 0.00 xxxx 807 ATOM 808 C VAL A 104 70.528 78.111 151.844 1.00 0.00 xxxx 808 ATOM 809 O VAL A 104 71.358 77.265 151.521 1.00 0.00 xxxx 809 ATOM 810 N TYR A 105 69.388 77.809 152.466 1.00 0.00 xxxx 810 ATOM 811 CA TYR A 105 69.059 76.444 152.853 1.00 0.00 xxxx 811 ATOM 812 CB TYR A 105 69.228 76.265 154.376 1.00 0.00 xxxx 812 ATOM 813 CG TYR A 105 70.671 76.389 154.807 1.00 0.00 xxxx 813 ATOM 814 CD1 TYR A 105 71.253 77.636 154.992 1.00 0.00 xxxx 814 ATOM 815 CE1 TYR A 105 72.581 77.756 155.351 1.00 0.00 xxxx 815 ATOM 816 CZ TYR A 105 73.346 76.619 155.527 1.00 0.00 xxxx 816 ATOM 817 OH TYR A 105 74.672 76.740 155.883 1.00 0.00 xxxx 817 ATOM 818 CE2 TYR A 105 72.793 75.365 155.342 1.00 0.00 xxxx 818 ATOM 819 CD2 TYR A 105 71.467 75.257 154.980 1.00 0.00 xxxx 819 ATOM 820 C TYR A 105 67.638 76.081 152.436 1.00 0.00 xxxx 820 ATOM 821 O TYR A 105 66.846 76.955 152.088 1.00 0.00 xxxx 821 ATOM 822 N TYR A 106 67.328 74.787 152.466 1.00 0.00 xxxx 822 ATOM 823 CA TYR A 106 65.968 74.320 152.202 1.00 0.00 xxxx 823 ATOM 824 CB TYR A 106 65.805 73.799 150.766 1.00 0.00 xxxx 824 ATOM 825 CG TYR A 106 64.400 73.263 150.542 1.00 0.00 xxxx 825 ATOM 826 CD1 TYR A 106 63.320 74.136 150.424 1.00 0.00 xxxx 826 ATOM 827 CE1 TYR A 106 62.021 73.665 150.254 1.00 0.00 xxxx 827 ATOM 828 CZ TYR A 106 61.779 72.307 150.206 1.00 0.00 xxxx 828 ATOM 829 OH TYR A 106 60.486 71.885 150.034 1.00 0.00 xxxx 829 ATOM 830 CE2 TYR A 106 62.821 71.409 150.321 1.00 0.00 xxxx 830 ATOM 831 CD2 TYR A 106 64.140 71.890 150.506 1.00 0.00 xxxx 831 ATOM 832 C TYR A 106 65.611 73.206 153.170 1.00 0.00 xxxx 832 ATOM 833 O TYR A 106 66.406 72.284 153.372 1.00 0.00 xxxx 833 ATOM 834 N VAL A 107 64.421 73.298 153.763 1.00 0.00 xxxx 834 ATOM 835 CA VAL A 107 63.878 72.225 154.590 1.00 0.00 xxxx 835 ATOM 836 CB VAL A 107 63.576 72.705 156.023 1.00 0.00 xxxx 836 ATOM 837 CG1 VAL A 107 62.977 71.559 156.841 1.00 0.00 xxxx 837 ATOM 838 CG2 VAL A 107 64.837 73.246 156.691 1.00 0.00 xxxx 838 ATOM 839 C VAL A 107 62.621 71.650 153.968 1.00 0.00 xxxx 839 ATOM 840 O VAL A 107 61.683 72.388 153.638 1.00 0.00 xxxx 840 ATOM 841 N GLY A 108 62.582 70.329 153.842 1.00 0.00 xxxx 841 ATOM 842 CA GLY A 108 61.396 69.675 153.322 1.00 0.00 xxxx 842 ATOM 843 C GLY A 108 61.471 68.179 153.492 1.00 0.00 xxxx 843 ATOM 844 O GLY A 108 61.937 67.673 154.513 1.00 0.00 xxxx 844 ATOM 845 N ALA A 109 61.009 67.467 152.473 1.00 0.00 xxxx 845 ATOM 846 CA ALA A 109 60.962 66.021 152.524 1.00 0.00 xxxx 846 ATOM 847 CB ALA A 109 59.693 65.555 153.212 1.00 0.00 xxxx 847 ATOM 848 C ALA A 109 61.050 65.499 151.101 1.00 0.00 xxxx 848 ATOM 849 O ALA A 109 60.772 66.233 150.154 1.00 0.00 xxxx 849 ATOM 850 N LYS A 110 61.447 64.244 150.951 1.00 0.00 xxxx 850 ATOM 851 CA LYS A 110 61.636 63.675 149.621 1.00 0.00 xxxx 851 ATOM 852 CB LYS A 110 62.642 62.528 149.664 1.00 0.00 xxxx 852 ATOM 853 CG LYS A 110 64.070 62.996 149.934 1.00 0.00 xxxx 853 ATOM 854 CD LYS A 110 64.508 63.980 148.850 1.00 0.00 xxxx 854 ATOM 855 CE LYS A 110 66.018 64.004 148.679 1.00 0.00 xxxx 855 ATOM 856 NZ LYS A 110 66.526 62.763 148.039 1.00 0.00 xxxx 856 ATOM 857 C LYS A 110 60.300 63.210 149.074 1.00 0.00 xxxx 857 ATOM 858 O LYS A 110 59.803 62.153 149.444 1.00 0.00 xxxx 858 ATOM 859 N ALA A 111 59.726 64.006 148.173 1.00 0.00 xxxx 859 ATOM 860 CA ALA A 111 58.378 63.731 147.687 1.00 0.00 xxxx 860 ATOM 861 CB ALA A 111 57.933 64.817 146.714 1.00 0.00 xxxx 861 ATOM 862 C ALA A 111 58.276 62.352 147.025 1.00 0.00 xxxx 862 ATOM 863 O ALA A 111 57.214 61.731 147.064 1.00 0.00 xxxx 863 ATOM 864 N GLU A 112 59.371 61.894 146.409 1.00 0.00 xxxx 864 ATOM 865 CA GLU A 112 59.416 60.558 145.815 1.00 0.00 xxxx 865 ATOM 866 C GLU A 112 59.013 59.494 146.832 1.00 0.00 xxxx 866 ATOM 867 O GLU A 112 58.281 58.552 146.520 1.00 0.00 xxxx 867 ATOM 868 CB GLU A 112 60.820 60.239 145.276 1.00 0.00 xxxx 868 ATOM 869 CG GLU A 112 61.342 61.190 144.209 1.00 0.00 xxxx 869 ATOM 870 CD GLU A 112 62.128 62.364 144.774 1.00 0.00 xxxx 870 ATOM 871 OE1 GLU A 112 61.879 62.772 145.933 1.00 0.00 xxxx 871 ATOM 872 OE2 GLU A 112 63.009 62.882 144.047 1.00 0.00 xxxx 872 ATOM 873 N GLN A 113 59.510 59.649 148.054 1.00 0.00 xxxx 873 ATOM 874 C GLN A 113 57.749 58.688 149.484 1.00 0.00 xxxx 874 ATOM 875 O GLN A 113 57.153 57.624 149.697 1.00 0.00 xxxx 875 ATOM 876 CA GLN A 113 59.241 58.715 149.144 1.00 0.00 xxxx 876 ATOM 877 CB GLN A 113 60.077 59.090 150.385 1.00 0.00 xxxx 877 ATOM 878 CG GLN A 113 59.812 58.227 151.626 1.00 0.00 xxxx 878 ATOM 879 CD GLN A 113 60.629 58.637 152.864 1.00 0.00 xxxx 879 ATOM 880 OE1 GLN A 113 60.781 59.826 153.183 1.00 0.00 xxxx 880 ATOM 881 NE2 GLN A 113 61.153 57.640 153.567 1.00 0.00 xxxx 881 ATOM 882 N SER A 114 57.135 59.870 149.559 1.00 0.00 xxxx 882 ATOM 883 CA SER A 114 55.708 59.885 149.877 1.00 0.00 xxxx 883 ATOM 884 CB SER A 114 55.192 61.303 150.175 1.00 0.00 xxxx 884 ATOM 885 OG SER A 114 55.337 62.195 149.078 1.00 0.00 xxxx 885 ATOM 886 C SER A 114 54.891 59.240 148.752 1.00 0.00 xxxx 886 ATOM 887 O SER A 114 53.912 58.554 149.022 1.00 0.00 xxxx 887 ATOM 888 N GLY A 115 55.302 59.440 147.504 1.00 0.00 xxxx 888 ATOM 889 CA GLY A 115 54.639 58.793 146.382 1.00 0.00 xxxx 889 ATOM 890 C GLY A 115 54.745 57.275 146.440 1.00 0.00 xxxx 890 ATOM 891 O GLY A 115 53.756 56.555 146.241 1.00 0.00 xxxx 891 ATOM 892 N ILE A 116 55.950 56.787 146.718 1.00 0.00 xxxx 892 ATOM 893 CA ILE A 116 56.167 55.351 146.855 1.00 0.00 xxxx 893 ATOM 894 CB ILE A 116 57.644 55.034 147.118 1.00 0.00 xxxx 894 ATOM 895 CG1 ILE A 116 58.482 55.388 145.876 1.00 0.00 xxxx 895 ATOM 896 CD1 ILE A 116 59.970 55.429 146.116 1.00 0.00 xxxx 896 ATOM 897 CG2 ILE A 116 57.816 53.563 147.498 1.00 0.00 xxxx 897 ATOM 898 C ILE A 116 55.285 54.778 147.960 1.00 0.00 xxxx 898 ATOM 899 O ILE A 116 54.631 53.756 147.766 1.00 0.00 xxxx 899 ATOM 900 N LEU A 117 55.258 55.431 149.120 1.00 0.00 xxxx 900 ATOM 901 CA LEU A 117 54.491 54.889 150.236 1.00 0.00 xxxx 901 ATOM 902 CB LEU A 117 54.789 55.673 151.520 1.00 0.00 xxxx 902 ATOM 903 CG LEU A 117 56.224 55.505 152.034 1.00 0.00 xxxx 903 ATOM 904 CD1 LEU A 117 56.507 56.501 153.152 1.00 0.00 xxxx 904 ATOM 905 CD2 LEU A 117 56.470 54.082 152.518 1.00 0.00 xxxx 905 ATOM 906 C LEU A 117 52.991 54.878 149.916 1.00 0.00 xxxx 906 ATOM 907 O LEU A 117 52.282 53.928 150.270 1.00 0.00 xxxx 907 ATOM 908 N GLN A 118 52.514 55.931 149.255 1.00 0.00 xxxx 908 ATOM 909 CA GLN A 118 51.141 55.976 148.746 1.00 0.00 xxxx 909 ATOM 910 CB GLN A 118 50.901 57.223 147.902 1.00 0.00 xxxx 910 ATOM 911 CG GLN A 118 50.449 58.426 148.646 1.00 0.00 xxxx 911 ATOM 912 CD GLN A 118 49.879 59.451 147.701 1.00 0.00 xxxx 912 ATOM 913 OE1 GLN A 118 50.580 59.948 146.809 1.00 0.00 xxxx 913 ATOM 914 NE2 GLN A 118 48.596 59.751 147.861 1.00 0.00 xxxx 914 ATOM 915 C GLN A 118 50.837 54.774 147.884 1.00 0.00 xxxx 915 ATOM 916 O GLN A 118 49.828 54.083 148.072 1.00 0.00 xxxx 916 ATOM 917 N GLY A 119 51.710 54.554 146.908 1.00 0.00 xxxx 917 ATOM 918 CA GLY A 119 51.531 53.469 145.958 1.00 0.00 xxxx 918 ATOM 919 C GLY A 119 51.496 52.113 146.637 1.00 0.00 xxxx 919 ATOM 920 O GLY A 119 50.727 51.240 146.249 1.00 0.00 xxxx 920 ATOM 921 N GLN A 120 52.328 51.939 147.659 1.00 0.00 xxxx 921 ATOM 922 CA GLN A 120 52.344 50.681 148.396 1.00 0.00 xxxx 922 ATOM 923 CB GLN A 120 53.474 50.671 149.420 1.00 0.00 xxxx 923 ATOM 924 CG GLN A 120 54.836 50.619 148.765 1.00 0.00 xxxx 924 ATOM 925 CD GLN A 120 55.953 50.609 149.768 1.00 0.00 xxxx 925 ATOM 926 OE1 GLN A 120 55.725 50.749 150.967 1.00 0.00 xxxx 926 ATOM 927 NE2 GLN A 120 57.179 50.439 149.284 1.00 0.00 xxxx 927 ATOM 928 C GLN A 120 51.007 50.421 149.087 1.00 0.00 xxxx 928 ATOM 929 O GLN A 120 50.520 49.297 149.080 1.00 0.00 xxxx 929 ATOM 930 N ILE A 121 50.424 51.463 149.674 1.00 0.00 xxxx 930 ATOM 931 CA ILE A 121 49.140 51.321 150.354 1.00 0.00 xxxx 931 ATOM 932 CB ILE A 121 48.686 52.659 150.977 1.00 0.00 xxxx 932 ATOM 933 CG1 ILE A 121 49.633 53.085 152.095 1.00 0.00 xxxx 933 ATOM 934 CD1 ILE A 121 49.463 54.550 152.512 1.00 0.00 xxxx 934 ATOM 935 CG2 ILE A 121 47.244 52.556 151.489 1.00 0.00 xxxx 935 ATOM 936 C ILE A 121 48.095 50.799 149.377 1.00 0.00 xxxx 936 ATOM 937 O ILE A 121 47.365 49.831 149.663 1.00 0.00 xxxx 937 ATOM 938 N MET A 122 48.027 51.433 148.213 1.00 0.00 xxxx 938 ATOM 939 CA MET A 122 47.014 51.056 147.233 1.00 0.00 xxxx 939 ATOM 940 CB MET A 122 46.928 52.108 146.118 1.00 0.00 xxxx 940 ATOM 941 CG MET A 122 45.735 51.898 145.188 1.00 0.00 xxxx 941 ATOM 942 SD MET A 122 44.169 52.297 146.002 1.00 0.00 xxxx 942 ATOM 943 CE MET A 122 44.193 54.082 145.894 1.00 0.00 xxxx 943 ATOM 944 C MET A 122 47.289 49.677 146.640 1.00 0.00 xxxx 944 ATOM 945 O MET A 122 46.362 48.898 146.428 1.00 0.00 xxxx 945 ATOM 946 N ALA A 123 48.557 49.374 146.366 1.00 0.00 xxxx 946 ATOM 947 CA ALA A 123 48.899 48.085 145.771 1.00 0.00 xxxx 947 ATOM 948 CB ALA A 123 50.363 48.040 145.366 1.00 0.00 xxxx 948 ATOM 949 C ALA A 123 48.590 46.950 146.730 1.00 0.00 xxxx 949 ATOM 950 O ALA A 123 48.059 45.914 146.332 1.00 0.00 xxxx 950 ATOM 951 N ASP A 124 48.920 47.150 148.000 1.00 0.00 xxxx 951 ATOM 952 CA ASP A 124 48.670 46.114 148.993 1.00 0.00 xxxx 952 ATOM 953 CB ASP A 124 49.330 46.479 150.319 1.00 0.00 xxxx 953 ATOM 954 CG ASP A 124 50.841 46.290 150.288 1.00 0.00 xxxx 954 ATOM 955 OD1 ASP A 124 51.333 45.512 149.430 1.00 0.00 xxxx 955 ATOM 956 OD2 ASP A 124 51.528 46.902 151.132 1.00 0.00 xxxx 956 ATOM 957 C ASP A 124 47.170 45.881 149.179 1.00 0.00 xxxx 957 ATOM 958 O ASP A 124 46.724 44.736 149.314 1.00 0.00 xxxx 958 ATOM 959 N TYR A 125 46.388 46.960 149.168 1.00 0.00 xxxx 959 ATOM 960 CA TYR A 125 44.936 46.818 149.209 1.00 0.00 xxxx 960 ATOM 961 CB TYR A 125 44.248 48.197 149.260 1.00 0.00 xxxx 961 ATOM 962 CG TYR A 125 42.757 48.059 149.036 1.00 0.00 xxxx 962 ATOM 963 CD1 TYR A 125 41.909 47.716 150.080 1.00 0.00 xxxx 963 ATOM 964 CE1 TYR A 125 40.544 47.555 149.867 1.00 0.00 xxxx 964 ATOM 965 CZ TYR A 125 40.038 47.721 148.584 1.00 0.00 xxxx 965 ATOM 966 OH TYR A 125 38.691 47.570 148.331 1.00 0.00 xxxx 966 ATOM 967 CE2 TYR A 125 40.867 48.050 147.541 1.00 0.00 xxxx 967 ATOM 968 CD2 TYR A 125 42.214 48.216 147.768 1.00 0.00 xxxx 968 ATOM 969 C TYR A 125 44.427 46.015 147.999 1.00 0.00 xxxx 969 ATOM 970 O TYR A 125 43.628 45.081 148.146 1.00 0.00 xxxx 970 ATOM 971 N TRP A 126 44.895 46.387 146.810 1.00 0.00 xxxx 971 ATOM 972 CA TRP A 126 44.453 45.762 145.565 1.00 0.00 xxxx 972 ATOM 973 CB TRP A 126 45.160 46.427 144.377 1.00 0.00 xxxx 973 ATOM 974 CG TRP A 126 44.797 45.873 143.033 1.00 0.00 xxxx 974 ATOM 975 CD1 TRP A 126 45.447 44.883 142.351 1.00 0.00 xxxx 975 ATOM 976 NE1 TRP A 126 44.821 44.649 141.150 1.00 0.00 xxxx 976 ATOM 977 CE2 TRP A 126 43.755 45.503 141.032 1.00 0.00 xxxx 977 ATOM 978 CD2 TRP A 126 43.709 46.289 142.199 1.00 0.00 xxxx 978 ATOM 979 CE3 TRP A 126 42.695 47.242 142.333 1.00 0.00 xxxx 979 ATOM 980 CZ3 TRP A 126 41.773 47.380 141.304 1.00 0.00 xxxx 980 ATOM 981 CH2 TRP A 126 41.849 46.584 140.159 1.00 0.00 xxxx 981 ATOM 982 CZ2 TRP A 126 42.829 45.642 140.001 1.00 0.00 xxxx 982 ATOM 983 C TRP A 126 44.722 44.254 145.590 1.00 0.00 xxxx 983 ATOM 984 O TRP A 126 43.852 43.445 145.266 1.00 0.00 xxxx 984 ATOM 985 N LYS A 127 45.926 43.882 146.013 1.00 0.00 xxxx 985 ATOM 986 CA LYS A 127 46.315 42.481 146.073 1.00 0.00 xxxx 986 ATOM 987 CB LYS A 127 47.795 42.368 146.436 1.00 0.00 xxxx 987 ATOM 988 CG LYS A 127 48.710 42.840 145.322 1.00 0.00 xxxx 988 ATOM 989 CD LYS A 127 50.162 42.861 145.766 1.00 0.00 xxxx 989 ATOM 990 CE LYS A 127 51.067 43.232 144.613 1.00 0.00 xxxx 990 ATOM 991 NZ LYS A 127 52.478 43.303 145.057 1.00 0.00 xxxx 991 ATOM 992 C LYS A 127 45.460 41.674 147.058 1.00 0.00 xxxx 992 ATOM 993 O LYS A 127 45.192 40.492 146.829 1.00 0.00 xxxx 993 ATOM 994 N ALA A 128 45.005 42.316 148.132 1.00 0.00 xxxx 994 ATOM 995 CA ALA A 128 44.264 41.614 149.176 1.00 0.00 xxxx 995 ATOM 996 CB ALA A 128 44.547 42.243 150.529 1.00 0.00 xxxx 996 ATOM 997 C ALA A 128 42.759 41.588 148.924 1.00 0.00 xxxx 997 ATOM 998 O ALA A 128 42.032 40.867 149.606 1.00 0.00 xxxx 998 ATOM 999 N HIS A 129 42.298 42.367 147.951 1.00 0.00 xxxx 999 ATOM 1000 CA HIS A 129 40.862 42.522 147.715 1.00 0.00 xxxx 1000 ATOM 1001 CB HIS A 129 40.403 43.904 148.198 1.00 0.00 xxxx 1001 ATOM 1002 CG HIS A 129 40.528 44.091 149.674 1.00 0.00 xxxx 1002 ATOM 1003 ND1 HIS A 129 41.703 44.486 150.278 1.00 0.00 xxxx 1003 ATOM 1004 CE1 HIS A 129 41.524 44.548 151.586 1.00 0.00 xxxx 1004 ATOM 1005 NE2 HIS A 129 40.280 44.196 151.854 1.00 0.00 xxxx 1005 ATOM 1006 CD2 HIS A 129 39.635 43.900 150.677 1.00 0.00 xxxx 1006 ATOM 1007 C HIS A 129 40.481 42.338 146.249 1.00 0.00 xxxx 1007 ATOM 1008 O HIS A 129 40.392 43.311 145.504 1.00 0.00 xxxx 1008 ATOM 1009 N PRO A 130 40.237 41.086 145.838 1.00 0.00 xxxx 1009 ATOM 1010 CA PRO A 130 39.859 40.757 144.457 1.00 0.00 xxxx 1010 ATOM 1011 CB PRO A 130 39.548 39.259 144.526 1.00 0.00 xxxx 1011 ATOM 1012 CG PRO A 130 40.266 38.768 145.740 1.00 0.00 xxxx 1012 ATOM 1013 CD PRO A 130 40.234 39.900 146.712 1.00 0.00 xxxx 1013 ATOM 1014 C PRO A 130 38.634 41.537 143.984 1.00 0.00 xxxx 1014 ATOM 1015 O PRO A 130 38.508 41.859 142.797 1.00 0.00 xxxx 1015 ATOM 1016 N GLU A 131 37.744 41.846 144.920 1.00 0.00 xxxx 1016 ATOM 1017 CA GLU A 131 36.507 42.546 144.601 1.00 0.00 xxxx 1017 ATOM 1018 CB GLU A 131 35.560 42.526 145.810 1.00 0.00 xxxx 1018 ATOM 1019 CG GLU A 131 35.970 43.431 146.972 1.00 0.00 xxxx 1019 ATOM 1020 CD GLU A 131 36.909 42.764 147.977 1.00 0.00 xxxx 1020 ATOM 1021 OE1 GLU A 131 37.546 41.737 147.647 1.00 0.00 xxxx 1021 ATOM 1022 OE2 GLU A 131 37.011 43.280 149.111 1.00 0.00 xxxx 1022 ATOM 1023 C GLU A 131 36.759 43.993 144.149 1.00 0.00 xxxx 1023 ATOM 1024 O GLU A 131 35.864 44.653 143.613 1.00 0.00 xxxx 1024 ATOM 1025 N ALA A 132 37.978 44.487 144.354 1.00 0.00 xxxx 1025 ATOM 1026 CA ALA A 132 38.301 45.870 143.999 1.00 0.00 xxxx 1026 ATOM 1027 CB ALA A 132 39.637 46.271 144.588 1.00 0.00 xxxx 1027 ATOM 1028 C ALA A 132 38.312 46.075 142.483 1.00 0.00 xxxx 1028 ATOM 1029 O ALA A 132 38.063 47.180 141.992 1.00 0.00 xxxx 1029 ATOM 1030 N ASP A 133 38.606 45.008 141.751 1.00 0.00 xxxx 1030 ATOM 1031 CA ASP A 133 38.589 45.039 140.296 1.00 0.00 xxxx 1031 ATOM 1032 CB ASP A 133 39.523 43.960 139.753 1.00 0.00 xxxx 1032 ATOM 1033 CG ASP A 133 39.634 43.977 138.253 1.00 0.00 xxxx 1033 ATOM 1034 OD1 ASP A 133 39.298 45.010 137.645 1.00 0.00 xxxx 1034 ATOM 1035 OD2 ASP A 133 40.082 42.949 137.695 1.00 0.00 xxxx 1035 ATOM 1036 C ASP A 133 37.141 44.847 139.833 1.00 0.00 xxxx 1036 ATOM 1037 O ASP A 133 36.727 43.749 139.436 1.00 0.00 xxxx 1037 ATOM 1038 N LYS A 134 36.381 45.936 139.891 1.00 0.00 xxxx 1038 ATOM 1039 C LYS A 134 34.486 45.450 138.329 1.00 0.00 xxxx 1039 ATOM 1040 O LYS A 134 33.414 44.858 138.173 1.00 0.00 xxxx 1040 ATOM 1041 CA LYS A 134 34.932 45.889 139.723 1.00 0.00 xxxx 1041 ATOM 1042 CB LYS A 134 34.341 47.257 140.067 1.00 0.00 xxxx 1042 ATOM 1043 CG LYS A 134 34.547 47.627 141.529 1.00 0.00 xxxx 1043 ATOM 1044 CD LYS A 134 34.923 49.089 141.712 1.00 0.00 xxxx 1044 ATOM 1045 CE LYS A 134 33.833 50.003 141.212 1.00 0.00 xxxx 1045 ATOM 1046 NZ LYS A 134 33.897 51.369 141.799 1.00 0.00 xxxx 1046 ATOM 1047 N ASN A 135 35.297 45.724 137.310 1.00 0.00 xxxx 1047 ATOM 1048 CA ASN A 135 34.922 45.292 135.961 1.00 0.00 xxxx 1048 ATOM 1049 CB ASN A 135 35.113 46.438 134.955 1.00 0.00 xxxx 1049 ATOM 1050 CG ASN A 135 36.566 46.696 134.618 1.00 0.00 xxxx 1050 ATOM 1051 OD1 ASN A 135 37.458 46.418 135.414 1.00 0.00 xxxx 1051 ATOM 1052 ND2 ASN A 135 36.813 47.232 133.425 1.00 0.00 xxxx 1052 ATOM 1053 C ASN A 135 35.693 44.043 135.519 1.00 0.00 xxxx 1053 ATOM 1054 O ASN A 135 35.605 43.631 134.364 1.00 0.00 xxxx 1054 ATOM 1055 N HIS A 136 36.439 43.448 136.450 1.00 0.00 xxxx 1055 ATOM 1056 CA HIS A 136 37.083 42.144 136.243 1.00 0.00 xxxx 1056 ATOM 1057 CB HIS A 136 36.021 41.045 136.121 1.00 0.00 xxxx 1057 ATOM 1058 CG HIS A 136 34.940 41.132 137.151 1.00 0.00 xxxx 1058 ATOM 1059 ND1 HIS A 136 35.154 40.840 138.482 1.00 0.00 xxxx 1059 ATOM 1060 CE1 HIS A 136 34.029 41.006 139.153 1.00 0.00 xxxx 1060 ATOM 1061 NE2 HIS A 136 33.090 41.389 138.305 1.00 0.00 xxxx 1061 ATOM 1062 CD2 HIS A 136 33.635 41.476 137.047 1.00 0.00 xxxx 1062 ATOM 1063 C HIS A 136 37.993 42.069 135.021 1.00 0.00 xxxx 1063 ATOM 1064 O HIS A 136 38.072 41.013 134.378 1.00 0.00 xxxx 1064 ATOM 1065 N ASP A 137 38.672 43.166 134.695 1.00 0.00 xxxx 1065 ATOM 1066 CA ASP A 137 39.557 43.181 133.529 1.00 0.00 xxxx 1066 ATOM 1067 CB ASP A 137 39.354 44.472 132.712 1.00 0.00 xxxx 1067 ATOM 1068 CG ASP A 137 39.756 45.740 133.464 1.00 0.00 xxxx 1068 ATOM 1069 OD1 ASP A 137 40.114 45.670 134.658 1.00 0.00 xxxx 1069 ATOM 1070 OD2 ASP A 137 39.711 46.818 132.834 1.00 0.00 xxxx 1070 ATOM 1071 C ASP A 137 41.033 43.012 133.892 1.00 0.00 xxxx 1071 ATOM 1072 O ASP A 137 41.893 43.016 133.011 1.00 0.00 xxxx 1072 ATOM 1073 N GLY A 138 41.320 42.860 135.183 1.00 0.00 xxxx 1073 ATOM 1074 CA GLY A 138 42.687 42.694 135.654 1.00 0.00 xxxx 1074 ATOM 1075 C GLY A 138 43.523 43.962 135.602 1.00 0.00 xxxx 1075 ATOM 1076 O GLY A 138 44.754 43.909 135.600 1.00 0.00 xxxx 1076 ATOM 1077 N VAL A 139 42.844 45.104 135.556 1.00 0.00 xxxx 1077 ATOM 1078 CA VAL A 139 43.486 46.412 135.479 1.00 0.00 xxxx 1078 ATOM 1079 CB VAL A 139 43.348 47.030 134.067 1.00 0.00 xxxx 1079 ATOM 1080 CG1 VAL A 139 44.016 48.399 134.003 1.00 0.00 xxxx 1080 ATOM 1081 CG2 VAL A 139 43.922 46.100 133.009 1.00 0.00 xxxx 1081 ATOM 1082 C VAL A 139 42.863 47.329 136.526 1.00 0.00 xxxx 1082 ATOM 1083 O VAL A 139 41.644 47.336 136.699 1.00 0.00 xxxx 1083 ATOM 1084 N MET A 140 43.691 48.096 137.228 1.00 0.00 xxxx 1084 ATOM 1085 CA MET A 140 43.187 49.070 138.191 1.00 0.00 xxxx 1085 ATOM 1086 CB MET A 140 44.219 49.322 139.293 1.00 0.00 xxxx 1086 ATOM 1087 CG MET A 140 43.815 50.406 140.290 1.00 0.00 xxxx 1087 ATOM 1088 SD MET A 140 45.208 50.999 141.305 1.00 0.00 xxxx 1088 ATOM 1089 CE MET A 140 45.540 49.546 142.295 1.00 0.00 xxxx 1089 ATOM 1090 C MET A 140 42.822 50.389 137.511 1.00 0.00 xxxx 1090 ATOM 1091 O MET A 140 43.702 51.147 137.098 1.00 0.00 xxxx 1091 ATOM 1092 N GLN A 141 41.525 50.655 137.382 1.00 0.00 xxxx 1092 ATOM 1093 CA GLN A 141 41.067 51.947 136.863 1.00 0.00 xxxx 1093 ATOM 1094 CB GLN A 141 39.638 51.857 136.329 1.00 0.00 xxxx 1094 ATOM 1095 CG GLN A 141 39.516 51.404 134.879 1.00 0.00 xxxx 1095 ATOM 1096 CD GLN A 141 39.714 49.912 134.703 1.00 0.00 xxxx 1096 ATOM 1097 OE1 GLN A 141 39.282 49.108 135.530 1.00 0.00 xxxx 1097 ATOM 1098 NE2 GLN A 141 40.352 49.531 133.602 1.00 0.00 xxxx 1098 ATOM 1099 C GLN A 141 41.121 52.998 137.958 1.00 0.00 xxxx 1099 ATOM 1100 O GLN A 141 40.443 52.855 138.974 1.00 0.00 xxxx 1100 ATOM 1101 N TYR A 142 41.888 54.065 137.752 1.00 0.00 xxxx 1101 ATOM 1102 CA TYR A 142 42.048 55.073 138.803 1.00 0.00 xxxx 1102 ATOM 1103 CB TYR A 142 43.434 54.948 139.458 1.00 0.00 xxxx 1103 ATOM 1104 CG TYR A 142 44.589 55.439 138.600 1.00 0.00 xxxx 1104 ATOM 1105 CD1 TYR A 142 45.024 56.767 138.666 1.00 0.00 xxxx 1105 ATOM 1106 CE1 TYR A 142 46.083 57.218 137.867 1.00 0.00 xxxx 1106 ATOM 1107 CZ TYR A 142 46.718 56.325 137.013 1.00 0.00 xxxx 1107 ATOM 1108 OH TYR A 142 47.762 56.736 136.211 1.00 0.00 xxxx 1108 ATOM 1109 CE2 TYR A 142 46.299 55.011 136.936 1.00 0.00 xxxx 1109 ATOM 1110 CD2 TYR A 142 45.249 54.574 137.728 1.00 0.00 xxxx 1110 ATOM 1111 C TYR A 142 41.857 56.500 138.303 1.00 0.00 xxxx 1111 ATOM 1112 O TYR A 142 41.923 56.769 137.102 1.00 0.00 xxxx 1112 ATOM 1113 N VAL A 143 41.623 57.415 139.242 1.00 0.00 xxxx 1113 ATOM 1114 CA VAL A 143 41.694 58.845 138.964 1.00 0.00 xxxx 1114 ATOM 1115 CB VAL A 143 40.337 59.563 139.132 1.00 0.00 xxxx 1115 ATOM 1116 CG1 VAL A 143 39.321 59.038 138.114 1.00 0.00 xxxx 1116 ATOM 1117 CG2 VAL A 143 39.815 59.418 140.565 1.00 0.00 xxxx 1117 ATOM 1118 C VAL A 143 42.743 59.449 139.882 1.00 0.00 xxxx 1118 ATOM 1119 O VAL A 143 43.052 58.898 140.939 1.00 0.00 xxxx 1119 ATOM 1120 N MET A 144 43.264 60.599 139.471 1.00 0.00 xxxx 1120 ATOM 1121 CA MET A 144 44.388 61.232 140.145 1.00 0.00 xxxx 1121 ATOM 1122 CB MET A 144 45.668 61.030 139.321 1.00 0.00 xxxx 1122 ATOM 1123 CG MET A 144 46.876 61.829 139.818 1.00 0.00 xxxx 1123 ATOM 1124 SD MET A 144 47.606 61.247 141.367 1.00 0.00 xxxx 1124 ATOM 1125 CE MET A 144 48.305 59.674 140.848 1.00 0.00 xxxx 1125 ATOM 1126 C MET A 144 44.118 62.717 140.359 1.00 0.00 xxxx 1126 ATOM 1127 O MET A 144 43.926 63.463 139.390 1.00 0.00 xxxx 1127 ATOM 1128 N LEU A 145 44.094 63.130 141.623 1.00 0.00 xxxx 1128 ATOM 1129 CA LEU A 145 43.927 64.537 141.981 1.00 0.00 xxxx 1129 ATOM 1130 CB LEU A 145 42.971 64.684 143.162 1.00 0.00 xxxx 1130 ATOM 1131 CG LEU A 145 41.522 64.394 142.788 1.00 0.00 xxxx 1131 ATOM 1132 CD1 LEU A 145 40.733 63.931 144.017 1.00 0.00 xxxx 1132 ATOM 1133 CD2 LEU A 145 40.908 65.648 142.174 1.00 0.00 xxxx 1133 ATOM 1134 C LEU A 145 45.291 65.124 142.311 1.00 0.00 xxxx 1134 ATOM 1135 O LEU A 145 45.892 64.771 143.333 1.00 0.00 xxxx 1135 ATOM 1136 N MET A 146 45.789 65.995 141.435 1.00 0.00 xxxx 1136 ATOM 1137 CA MET A 146 47.123 66.570 141.610 1.00 0.00 xxxx 1137 ATOM 1138 CB MET A 146 47.793 66.784 140.258 1.00 0.00 xxxx 1138 ATOM 1139 CG MET A 146 47.928 65.499 139.472 1.00 0.00 xxxx 1139 ATOM 1140 SD MET A 146 48.716 65.741 137.878 1.00 0.00 xxxx 1140 ATOM 1141 CE MET A 146 47.451 66.667 136.991 1.00 0.00 xxxx 1141 ATOM 1142 C MET A 146 47.070 67.882 142.377 1.00 0.00 xxxx 1142 ATOM 1143 O MET A 146 46.039 68.531 142.425 1.00 0.00 xxxx 1143 ATOM 1144 N GLY A 147 48.197 68.261 142.974 1.00 0.00 xxxx 1144 ATOM 1145 CA GLY A 147 48.327 69.550 143.634 1.00 0.00 xxxx 1145 ATOM 1146 C GLY A 147 48.417 70.715 142.657 1.00 0.00 xxxx 1146 ATOM 1147 O GLY A 147 47.771 70.705 141.619 1.00 0.00 xxxx 1147 ATOM 1148 N GLN A 148 49.205 71.732 142.986 1.00 0.00 xxxx 1148 ATOM 1149 CA GLN A 148 49.395 72.843 142.055 1.00 0.00 xxxx 1149 ATOM 1150 CB GLN A 148 49.902 74.083 142.796 1.00 0.00 xxxx 1150 ATOM 1151 CG GLN A 148 48.868 74.706 143.724 1.00 0.00 xxxx 1151 ATOM 1152 CD GLN A 148 49.487 75.729 144.659 1.00 0.00 xxxx 1152 ATOM 1153 OE1 GLN A 148 50.471 75.444 145.347 1.00 0.00 xxxx 1153 ATOM 1154 NE2 GLN A 148 48.921 76.939 144.678 1.00 0.00 xxxx 1154 ATOM 1155 C GLN A 148 50.374 72.477 140.953 1.00 0.00 xxxx 1155 ATOM 1156 O GLN A 148 51.385 71.828 141.210 1.00 0.00 xxxx 1156 ATOM 1157 N PRO A 149 50.104 72.936 139.721 1.00 0.00 xxxx 1157 ATOM 1158 CA PRO A 149 51.021 72.653 138.610 1.00 0.00 xxxx 1158 ATOM 1159 CB PRO A 149 50.440 73.464 137.451 1.00 0.00 xxxx 1159 ATOM 1160 CG PRO A 149 49.015 73.676 137.798 1.00 0.00 xxxx 1160 ATOM 1161 CD PRO A 149 48.921 73.696 139.294 1.00 0.00 xxxx 1161 ATOM 1162 C PRO A 149 52.447 73.111 138.915 1.00 0.00 xxxx 1162 ATOM 1163 O PRO A 149 52.656 74.234 139.367 1.00 0.00 xxxx 1163 ATOM 1164 N GLY A 150 53.414 72.235 138.687 1.00 0.00 xxxx 1164 ATOM 1165 CA GLY A 150 54.802 72.622 138.876 1.00 0.00 xxxx 1165 ATOM 1166 C GLY A 150 55.350 72.563 140.290 1.00 0.00 xxxx 1166 ATOM 1167 O GLY A 150 56.548 72.731 140.491 1.00 0.00 xxxx 1167 ATOM 1168 N HIS A 151 54.485 72.346 141.271 1.00 0.00 xxxx 1168 ATOM 1169 CA HIS A 151 54.938 72.119 142.640 1.00 0.00 xxxx 1169 ATOM 1170 CB HIS A 151 53.705 72.145 143.550 1.00 0.00 xxxx 1170 ATOM 1171 CG HIS A 151 53.984 72.117 145.018 1.00 0.00 xxxx 1171 ATOM 1172 ND1 HIS A 151 54.669 71.099 145.648 1.00 0.00 xxxx 1172 ATOM 1173 CE1 HIS A 151 54.689 71.325 146.947 1.00 0.00 xxxx 1173 ATOM 1174 NE2 HIS A 151 54.032 72.449 147.188 1.00 0.00 xxxx 1174 ATOM 1175 CD2 HIS A 151 53.580 72.963 146.001 1.00 0.00 xxxx 1175 ATOM 1176 C HIS A 151 55.671 70.774 142.681 1.00 0.00 xxxx 1176 ATOM 1177 O HIS A 151 55.152 69.796 142.145 1.00 0.00 xxxx 1177 ATOM 1178 N GLN A 152 56.857 70.706 143.293 1.00 0.00 xxxx 1178 ATOM 1179 CA GLN A 152 57.634 69.455 143.237 1.00 0.00 xxxx 1179 ATOM 1180 CB GLN A 152 59.023 69.636 143.877 1.00 0.00 xxxx 1180 ATOM 1181 CG GLN A 152 59.071 69.521 145.405 1.00 0.00 xxxx 1181 ATOM 1182 CD GLN A 152 58.525 70.739 146.127 1.00 0.00 xxxx 1182 ATOM 1183 OE1 GLN A 152 58.442 71.832 145.566 1.00 0.00 xxxx 1183 ATOM 1184 NE2 GLN A 152 58.159 70.552 147.391 1.00 0.00 xxxx 1184 ATOM 1185 C GLN A 152 56.899 68.263 143.880 1.00 0.00 xxxx 1185 ATOM 1186 O GLN A 152 57.065 67.118 143.452 1.00 0.00 xxxx 1186 ATOM 1187 N ASP A 153 56.078 68.516 144.891 1.00 0.00 xxxx 1187 ATOM 1188 CA ASP A 153 55.357 67.426 145.527 1.00 0.00 xxxx 1188 ATOM 1189 CB ASP A 153 54.754 67.867 146.859 1.00 0.00 xxxx 1189 ATOM 1190 CG ASP A 153 55.813 68.166 147.909 1.00 0.00 xxxx 1190 ATOM 1191 OD1 ASP A 153 56.988 67.774 147.732 1.00 0.00 xxxx 1191 ATOM 1192 OD2 ASP A 153 55.472 68.791 148.934 1.00 0.00 xxxx 1192 ATOM 1193 C ASP A 153 54.257 66.902 144.617 1.00 0.00 xxxx 1193 ATOM 1194 O ASP A 153 53.980 65.708 144.612 1.00 0.00 xxxx 1194 ATOM 1195 N ALA A 154 53.627 67.791 143.852 1.00 0.00 xxxx 1195 ATOM 1196 CA ALA A 154 52.591 67.356 142.925 1.00 0.00 xxxx 1196 ATOM 1197 CB ALA A 154 51.830 68.554 142.337 1.00 0.00 xxxx 1197 ATOM 1198 C ALA A 154 53.233 66.521 141.820 1.00 0.00 xxxx 1198 ATOM 1199 O ALA A 154 52.750 65.438 141.503 1.00 0.00 xxxx 1199 ATOM 1200 N ILE A 155 54.338 67.008 141.258 1.00 0.00 xxxx 1200 ATOM 1201 CA ILE A 155 55.012 66.292 140.177 1.00 0.00 xxxx 1201 ATOM 1202 CB ILE A 155 56.235 67.079 139.660 1.00 0.00 xxxx 1202 ATOM 1203 CG1 ILE A 155 55.791 68.403 139.039 1.00 0.00 xxxx 1203 ATOM 1204 CD1 ILE A 155 56.916 69.404 138.848 1.00 0.00 xxxx 1204 ATOM 1205 CG2 ILE A 155 57.012 66.273 138.618 1.00 0.00 xxxx 1205 ATOM 1206 C ILE A 155 55.431 64.905 140.652 1.00 0.00 xxxx 1206 ATOM 1207 O ILE A 155 55.131 63.892 140.014 1.00 0.00 xxxx 1207 ATOM 1208 N LEU A 156 56.125 64.864 141.785 1.00 0.00 xxxx 1208 ATOM 1209 CA LEU A 156 56.755 63.617 142.208 1.00 0.00 xxxx 1209 ATOM 1210 CB LEU A 156 57.933 63.924 143.141 1.00 0.00 xxxx 1210 ATOM 1211 CG LEU A 156 59.079 64.620 142.408 1.00 0.00 xxxx 1211 ATOM 1212 CD1 LEU A 156 60.088 65.153 143.415 1.00 0.00 xxxx 1212 ATOM 1213 CD2 LEU A 156 59.740 63.664 141.396 1.00 0.00 xxxx 1213 ATOM 1214 C LEU A 156 55.776 62.638 142.868 1.00 0.00 xxxx 1214 ATOM 1215 O LEU A 156 55.900 61.428 142.671 1.00 0.00 xxxx 1215 ATOM 1216 N ARG A 157 54.800 63.124 143.631 1.00 0.00 xxxx 1216 ATOM 1217 CA ARG A 157 53.834 62.195 144.216 1.00 0.00 xxxx 1217 ATOM 1218 CB ARG A 157 52.940 62.892 145.235 1.00 0.00 xxxx 1218 ATOM 1219 CG ARG A 157 53.664 63.219 146.531 1.00 0.00 xxxx 1219 ATOM 1220 CD ARG A 157 52.800 64.102 147.399 1.00 0.00 xxxx 1220 ATOM 1221 NE ARG A 157 53.528 64.587 148.570 1.00 0.00 xxxx 1221 ATOM 1222 CZ ARG A 157 53.102 65.579 149.343 1.00 0.00 xxxx 1222 ATOM 1223 NH1 ARG A 157 51.958 66.183 149.071 1.00 0.00 xxxx 1223 ATOM 1224 NH2 ARG A 157 53.823 65.977 150.380 1.00 0.00 xxxx 1224 ATOM 1225 C ARG A 157 52.995 61.548 143.128 1.00 0.00 xxxx 1225 ATOM 1226 O ARG A 157 52.681 60.361 143.205 1.00 0.00 xxxx 1226 ATOM 1227 N THR A 158 52.654 62.321 142.104 1.00 0.00 xxxx 1227 ATOM 1228 CA THR A 158 51.861 61.804 140.992 1.00 0.00 xxxx 1228 ATOM 1229 CB THR A 158 51.466 62.932 140.027 1.00 0.00 xxxx 1229 ATOM 1230 OG1 THR A 158 50.646 63.877 140.737 1.00 0.00 xxxx 1230 ATOM 1231 CG2 THR A 158 50.680 62.386 138.858 1.00 0.00 xxxx 1231 ATOM 1232 C THR A 158 52.626 60.721 140.239 1.00 0.00 xxxx 1232 ATOM 1233 O THR A 158 52.078 59.654 139.931 1.00 0.00 xxxx 1233 ATOM 1234 N GLN A 159 53.896 60.997 139.954 1.00 0.00 xxxx 1234 ATOM 1235 CA GLN A 159 54.742 60.073 139.220 1.00 0.00 xxxx 1235 ATOM 1236 CB GLN A 159 56.065 60.756 138.868 1.00 0.00 xxxx 1236 ATOM 1237 CG GLN A 159 57.079 59.851 138.200 1.00 0.00 xxxx 1237 ATOM 1238 CD GLN A 159 58.397 60.554 137.958 1.00 0.00 xxxx 1238 ATOM 1239 OE1 GLN A 159 58.507 61.772 138.132 1.00 0.00 xxxx 1239 ATOM 1240 NE2 GLN A 159 59.411 59.789 137.566 1.00 0.00 xxxx 1240 ATOM 1241 C GLN A 159 55.002 58.794 140.016 1.00 0.00 xxxx 1241 ATOM 1242 O GLN A 159 54.830 57.686 139.506 1.00 0.00 xxxx 1242 ATOM 1243 N TYR A 160 55.436 58.943 141.261 1.00 0.00 xxxx 1243 ATOM 1244 CA TYR A 160 55.930 57.774 141.985 1.00 0.00 xxxx 1244 ATOM 1245 CB TYR A 160 56.932 58.207 143.074 1.00 0.00 xxxx 1245 ATOM 1246 CG TYR A 160 58.324 58.434 142.513 1.00 0.00 xxxx 1246 ATOM 1247 CD1 TYR A 160 58.656 59.629 141.880 1.00 0.00 xxxx 1247 ATOM 1248 CE1 TYR A 160 59.922 59.829 141.345 1.00 0.00 xxxx 1248 ATOM 1249 CZ TYR A 160 60.872 58.831 141.445 1.00 0.00 xxxx 1249 ATOM 1250 OH TYR A 160 62.141 59.022 140.925 1.00 0.00 xxxx 1250 ATOM 1251 CE2 TYR A 160 60.565 57.634 142.059 1.00 0.00 xxxx 1251 ATOM 1252 CD2 TYR A 160 59.292 57.440 142.587 1.00 0.00 xxxx 1252 ATOM 1253 C TYR A 160 54.823 56.906 142.578 1.00 0.00 xxxx 1253 ATOM 1254 O TYR A 160 55.029 55.709 142.755 1.00 0.00 xxxx 1254 ATOM 1255 N SER A 161 53.653 57.473 142.867 1.00 0.00 xxxx 1255 ATOM 1256 CA SER A 161 52.555 56.642 143.365 1.00 0.00 xxxx 1256 ATOM 1257 CB SER A 161 51.334 57.481 143.755 1.00 0.00 xxxx 1257 ATOM 1258 OG SER A 161 50.896 58.302 142.672 1.00 0.00 xxxx 1258 ATOM 1259 C SER A 161 52.170 55.606 142.317 1.00 0.00 xxxx 1259 ATOM 1260 O SER A 161 52.085 54.412 142.615 1.00 0.00 xxxx 1260 ATOM 1261 N ILE A 162 51.975 56.056 141.081 1.00 0.00 xxxx 1261 ATOM 1262 CA ILE A 162 51.519 55.152 140.043 1.00 0.00 xxxx 1262 ATOM 1263 CB ILE A 162 50.948 55.919 138.835 1.00 0.00 xxxx 1263 ATOM 1264 CG1 ILE A 162 49.767 56.797 139.266 1.00 0.00 xxxx 1264 ATOM 1265 CD1 ILE A 162 48.691 56.079 140.082 1.00 0.00 xxxx 1265 ATOM 1266 CG2 ILE A 162 50.522 54.942 137.737 1.00 0.00 xxxx 1266 ATOM 1267 C ILE A 162 52.650 54.215 139.615 1.00 0.00 xxxx 1267 ATOM 1268 O ILE A 162 52.418 53.028 139.407 1.00 0.00 xxxx 1268 ATOM 1269 N GLN A 163 53.876 54.725 139.497 1.00 0.00 xxxx 1269 ATOM 1270 CA GLN A 163 54.979 53.845 139.124 1.00 0.00 xxxx 1270 ATOM 1271 CB GLN A 163 56.292 54.614 138.981 1.00 0.00 xxxx 1271 ATOM 1272 CG GLN A 163 57.425 53.743 138.413 1.00 0.00 xxxx 1272 ATOM 1273 CD GLN A 163 57.069 53.143 137.053 1.00 0.00 xxxx 1273 ATOM 1274 OE1 GLN A 163 56.595 53.845 136.160 1.00 0.00 xxxx 1274 ATOM 1275 NE2 GLN A 163 57.275 51.836 136.903 1.00 0.00 xxxx 1275 ATOM 1276 C GLN A 163 55.141 52.726 140.150 1.00 0.00 xxxx 1276 ATOM 1277 O GLN A 163 55.471 51.597 139.790 1.00 0.00 xxxx 1277 ATOM 1278 N THR A 164 54.865 53.035 141.418 1.00 0.00 xxxx 1278 ATOM 1279 CA THR A 164 55.003 52.045 142.476 1.00 0.00 xxxx 1279 ATOM 1280 CB THR A 164 54.952 52.716 143.864 1.00 0.00 xxxx 1280 ATOM 1281 OG1 THR A 164 56.123 53.530 144.020 1.00 0.00 xxxx 1281 ATOM 1282 CG2 THR A 164 54.924 51.673 144.980 1.00 0.00 xxxx 1282 ATOM 1283 C THR A 164 53.940 50.949 142.361 1.00 0.00 xxxx 1283 ATOM 1284 O THR A 164 54.239 49.769 142.563 1.00 0.00 xxxx 1284 ATOM 1285 N VAL A 165 52.712 51.338 142.017 1.00 0.00 xxxx 1285 ATOM 1286 CA VAL A 165 51.667 50.354 141.732 1.00 0.00 xxxx 1286 ATOM 1287 CB VAL A 165 50.323 51.038 141.438 1.00 0.00 xxxx 1287 ATOM 1288 CG1 VAL A 165 49.261 49.993 141.094 1.00 0.00 xxxx 1288 ATOM 1289 CG2 VAL A 165 49.889 51.838 142.653 1.00 0.00 xxxx 1289 ATOM 1290 C VAL A 165 52.081 49.447 140.565 1.00 0.00 xxxx 1290 ATOM 1291 O VAL A 165 51.934 48.224 140.647 1.00 0.00 xxxx 1291 ATOM 1292 N LYS A 166 52.596 50.028 139.482 1.00 0.00 xxxx 1292 ATOM 1293 CA LYS A 166 53.042 49.206 138.357 1.00 0.00 xxxx 1293 ATOM 1294 CB LYS A 166 53.510 50.065 137.180 1.00 0.00 xxxx 1294 ATOM 1295 CG LYS A 166 52.445 50.933 136.540 1.00 0.00 xxxx 1295 ATOM 1296 CD LYS A 166 53.072 51.745 135.414 1.00 0.00 xxxx 1296 ATOM 1297 CE LYS A 166 52.078 52.671 134.758 1.00 0.00 xxxx 1297 ATOM 1298 NZ LYS A 166 52.729 53.514 133.706 1.00 0.00 xxxx 1298 ATOM 1299 C LYS A 166 54.179 48.276 138.777 1.00 0.00 xxxx 1299 ATOM 1300 O LYS A 166 54.214 47.105 138.386 1.00 0.00 xxxx 1300 ATOM 1301 N ASP A 167 55.107 48.802 139.571 1.00 0.00 xxxx 1301 ATOM 1302 CA ASP A 167 56.255 48.020 140.029 1.00 0.00 xxxx 1302 ATOM 1303 CB ASP A 167 57.224 48.907 140.805 1.00 0.00 xxxx 1303 ATOM 1304 CG ASP A 167 57.973 49.879 139.907 1.00 0.00 xxxx 1304 ATOM 1305 OD1 ASP A 167 57.921 49.715 138.667 1.00 0.00 xxxx 1305 ATOM 1306 OD2 ASP A 167 58.618 50.801 140.447 1.00 0.00 xxxx 1306 ATOM 1307 C ASP A 167 55.820 46.832 140.892 1.00 0.00 xxxx 1307 ATOM 1308 O ASP A 167 56.531 45.832 140.998 1.00 0.00 xxxx 1308 ATOM 1309 N ALA A 168 54.642 46.951 141.502 1.00 0.00 xxxx 1309 ATOM 1310 CA ALA A 168 54.075 45.895 142.326 1.00 0.00 xxxx 1310 ATOM 1311 CB ALA A 168 53.060 46.481 143.302 1.00 0.00 xxxx 1311 ATOM 1312 C ALA A 168 53.428 44.798 141.477 1.00 0.00 xxxx 1312 ATOM 1313 O ALA A 168 52.883 43.830 142.008 1.00 0.00 xxxx 1313 ATOM 1314 N GLY A 169 53.476 44.965 140.157 1.00 0.00 xxxx 1314 ATOM 1315 CA GLY A 169 52.955 43.965 139.241 1.00 0.00 xxxx 1315 ATOM 1316 C GLY A 169 51.511 44.173 138.819 1.00 0.00 xxxx 1316 ATOM 1317 O GLY A 169 50.890 43.274 138.249 1.00 0.00 xxxx 1317 ATOM 1318 N ILE A 170 50.979 45.360 139.091 1.00 0.00 xxxx 1318 ATOM 1319 CA ILE A 170 49.571 45.657 138.823 1.00 0.00 xxxx 1319 ATOM 1320 CB ILE A 170 48.918 46.348 140.042 1.00 0.00 xxxx 1320 ATOM 1321 CG1 ILE A 170 48.984 45.434 141.273 1.00 0.00 xxxx 1321 ATOM 1322 CD1 ILE A 170 48.785 46.204 142.574 1.00 0.00 xxxx 1322 ATOM 1323 CG2 ILE A 170 47.468 46.788 139.749 1.00 0.00 xxxx 1323 ATOM 1324 C ILE A 170 49.440 46.523 137.575 1.00 0.00 xxxx 1324 ATOM 1325 O ILE A 170 50.110 47.543 137.457 1.00 0.00 xxxx 1325 ATOM 1326 N LYS A 171 48.578 46.111 136.647 1.00 0.00 xxxx 1326 ATOM 1327 CA LYS A 171 48.273 46.927 135.474 1.00 0.00 xxxx 1327 ATOM 1328 CB LYS A 171 47.663 46.079 134.357 1.00 0.00 xxxx 1328 ATOM 1329 CG LYS A 171 48.611 45.042 133.779 1.00 0.00 xxxx 1329 ATOM 1330 CD LYS A 171 47.900 44.207 132.722 1.00 0.00 xxxx 1330 ATOM 1331 CE LYS A 171 48.757 43.051 132.242 1.00 0.00 xxxx 1331 ATOM 1332 NZ LYS A 171 47.987 42.147 131.340 1.00 0.00 xxxx 1332 ATOM 1333 C LYS A 171 47.314 48.042 135.859 1.00 0.00 xxxx 1333 ATOM 1334 O LYS A 171 46.385 47.832 136.642 1.00 0.00 xxxx 1334 ATOM 1335 N VAL A 172 47.536 49.231 135.310 1.00 0.00 xxxx 1335 ATOM 1336 CA VAL A 172 46.716 50.378 135.681 1.00 0.00 xxxx 1336 ATOM 1337 CB VAL A 172 47.507 51.384 136.554 1.00 0.00 xxxx 1337 ATOM 1338 CG1 VAL A 172 48.094 50.686 137.780 1.00 0.00 xxxx 1338 ATOM 1339 CG2 VAL A 172 48.598 52.069 135.743 1.00 0.00 xxxx 1339 ATOM 1340 C VAL A 172 46.164 51.080 134.451 1.00 0.00 xxxx 1340 ATOM 1341 O VAL A 172 46.700 50.963 133.346 1.00 0.00 xxxx 1341 ATOM 1342 N GLN A 173 45.080 51.818 134.661 1.00 0.00 xxxx 1342 ATOM 1343 CA GLN A 173 44.502 52.657 133.631 1.00 0.00 xxxx 1343 ATOM 1344 CB GLN A 173 43.334 51.963 132.930 1.00 0.00 xxxx 1344 ATOM 1345 CG GLN A 173 42.782 52.813 131.799 1.00 0.00 xxxx 1345 ATOM 1346 CD GLN A 173 41.612 52.175 131.091 1.00 0.00 xxxx 1346 ATOM 1347 OE1 GLN A 173 40.758 51.538 131.713 1.00 0.00 xxxx 1347 ATOM 1348 NE2 GLN A 173 41.567 52.334 129.773 1.00 0.00 xxxx 1348 ATOM 1349 C GLN A 173 44.033 53.957 134.253 1.00 0.00 xxxx 1349 ATOM 1350 O GLN A 173 43.168 53.956 135.129 1.00 0.00 xxxx 1350 ATOM 1351 N GLU A 174 44.604 55.060 133.783 1.00 0.00 xxxx 1351 ATOM 1352 CA GLU A 174 44.240 56.389 134.240 1.00 0.00 xxxx 1352 ATOM 1353 CB GLU A 174 45.385 57.356 133.963 1.00 0.00 xxxx 1353 ATOM 1354 CG GLU A 174 45.220 58.707 134.592 1.00 0.00 xxxx 1354 ATOM 1355 CD GLU A 174 46.487 59.534 134.440 1.00 0.00 xxxx 1355 ATOM 1356 OE1 GLU A 174 46.579 60.296 133.463 1.00 0.00 xxxx 1356 ATOM 1357 OE2 GLU A 174 47.400 59.384 135.278 1.00 0.00 xxxx 1357 ATOM 1358 C GLU A 174 42.967 56.881 133.552 1.00 0.00 xxxx 1358 ATOM 1359 O GLU A 174 42.996 57.233 132.374 1.00 0.00 xxxx 1359 ATOM 1360 N LEU A 175 41.852 56.899 134.274 1.00 0.00 xxxx 1360 ATOM 1361 CA LEU A 175 40.604 57.387 133.681 1.00 0.00 xxxx 1361 ATOM 1362 CB LEU A 175 39.398 56.922 134.498 1.00 0.00 xxxx 1362 ATOM 1363 CG LEU A 175 39.121 55.423 134.515 1.00 0.00 xxxx 1363 ATOM 1364 CD1 LEU A 175 37.913 55.154 135.402 1.00 0.00 xxxx 1364 ATOM 1365 CD2 LEU A 175 38.873 54.925 133.104 1.00 0.00 xxxx 1365 ATOM 1366 C LEU A 175 40.586 58.906 133.569 1.00 0.00 xxxx 1366 ATOM 1367 O LEU A 175 40.021 59.462 132.624 1.00 0.00 xxxx 1367 ATOM 1368 N ALA A 176 41.186 59.574 134.550 1.00 0.00 xxxx 1368 ATOM 1369 CA ALA A 176 41.232 61.036 134.576 1.00 0.00 xxxx 1369 ATOM 1370 CB ALA A 176 39.880 61.605 134.965 1.00 0.00 xxxx 1370 ATOM 1371 C ALA A 176 42.285 61.520 135.544 1.00 0.00 xxxx 1371 ATOM 1372 O ALA A 176 42.571 60.864 136.535 1.00 0.00 xxxx 1372 ATOM 1373 N LYS A 177 42.860 62.676 135.254 1.00 0.00 xxxx 1373 ATOM 1374 CA LYS A 177 43.719 63.346 136.213 1.00 0.00 xxxx 1374 ATOM 1375 CB LYS A 177 45.181 62.923 136.061 1.00 0.00 xxxx 1375 ATOM 1376 CG LYS A 177 45.871 63.428 134.814 1.00 0.00 xxxx 1376 ATOM 1377 CD LYS A 177 47.373 63.195 134.903 1.00 0.00 xxxx 1377 ATOM 1378 CE LYS A 177 48.041 63.494 133.577 1.00 0.00 xxxx 1378 ATOM 1379 NZ LYS A 177 49.468 63.096 133.605 1.00 0.00 xxxx 1379 ATOM 1380 C LYS A 177 43.561 64.833 136.011 1.00 0.00 xxxx 1380 ATOM 1381 O LYS A 177 43.310 65.291 134.901 1.00 0.00 xxxx 1381 ATOM 1382 N ASP A 178 43.663 65.595 137.089 1.00 0.00 xxxx 1382 ATOM 1383 CA ASP A 178 43.572 67.044 136.961 1.00 0.00 xxxx 1383 ATOM 1384 CB ASP A 178 42.114 67.492 136.772 1.00 0.00 xxxx 1384 ATOM 1385 CG ASP A 178 41.987 68.845 136.073 1.00 0.00 xxxx 1385 ATOM 1386 OD1 ASP A 178 43.015 69.536 135.869 1.00 0.00 xxxx 1386 ATOM 1387 OD2 ASP A 178 40.839 69.229 135.735 1.00 0.00 xxxx 1387 ATOM 1388 C ASP A 178 44.166 67.669 138.200 1.00 0.00 xxxx 1388 ATOM 1389 O ASP A 178 44.343 67.010 139.226 1.00 0.00 xxxx 1389 ATOM 1390 N TYR A 179 44.462 68.956 138.084 1.00 0.00 xxxx 1390 ATOM 1391 CA TYR A 179 44.969 69.751 139.184 1.00 0.00 xxxx 1391 ATOM 1392 CB TYR A 179 45.795 70.923 138.647 1.00 0.00 xxxx 1392 ATOM 1393 CG TYR A 179 47.028 70.506 137.884 1.00 0.00 xxxx 1393 ATOM 1394 CD1 TYR A 179 48.176 70.081 138.553 1.00 0.00 xxxx 1394 ATOM 1395 CE1 TYR A 179 49.308 69.699 137.851 1.00 0.00 xxxx 1395 ATOM 1396 CZ TYR A 179 49.294 69.751 136.473 1.00 0.00 xxxx 1396 ATOM 1397 OH TYR A 179 50.413 69.378 135.756 1.00 0.00 xxxx 1397 ATOM 1398 CE2 TYR A 179 48.175 70.174 135.792 1.00 0.00 xxxx 1398 ATOM 1399 CD2 TYR A 179 47.049 70.545 136.495 1.00 0.00 xxxx 1399 ATOM 1400 C TYR A 179 43.834 70.278 140.038 1.00 0.00 xxxx 1400 ATOM 1401 O TYR A 179 42.921 70.928 139.524 1.00 0.00 xxxx 1401 ATOM 1402 N ALA A 180 43.899 70.014 141.344 1.00 0.00 xxxx 1402 ATOM 1403 CA ALA A 180 42.958 70.631 142.268 1.00 0.00 xxxx 1403 ATOM 1404 CB ALA A 180 42.086 69.574 142.946 1.00 0.00 xxxx 1404 ATOM 1405 C ALA A 180 43.674 71.497 143.305 1.00 0.00 xxxx 1405 ATOM 1406 O ALA A 180 43.052 71.949 144.258 1.00 0.00 xxxx 1406 ATOM 1407 N ASN A 181 44.977 71.723 143.111 1.00 0.00 xxxx 1407 ATOM 1408 CA ASN A 181 45.678 72.840 143.766 1.00 0.00 xxxx 1408 ATOM 1409 CB ASN A 181 45.029 74.165 143.361 1.00 0.00 xxxx 1409 ATOM 1410 CG ASN A 181 44.936 74.317 141.862 1.00 0.00 xxxx 1410 ATOM 1411 OD1 ASN A 181 45.904 74.057 141.140 1.00 0.00 xxxx 1411 ATOM 1412 ND2 ASN A 181 43.759 74.698 141.378 1.00 0.00 xxxx 1412 ATOM 1413 C ASN A 181 45.728 72.755 145.284 1.00 0.00 xxxx 1413 ATOM 1414 O ASN A 181 45.785 73.792 145.959 1.00 0.00 xxxx 1414 ATOM 1415 N TRP A 182 45.695 71.520 145.796 1.00 0.00 xxxx 1415 ATOM 1416 CA TRP A 182 45.769 71.207 147.235 1.00 0.00 xxxx 1416 ATOM 1417 CB TRP A 182 46.918 71.965 147.932 1.00 0.00 xxxx 1417 ATOM 1418 CG TRP A 182 48.266 71.865 147.262 1.00 0.00 xxxx 1418 ATOM 1419 CD1 TRP A 182 49.010 72.896 146.766 1.00 0.00 xxxx 1419 ATOM 1420 NE1 TRP A 182 50.186 72.424 146.240 1.00 0.00 xxxx 1420 ATOM 1421 CE2 TRP A 182 50.237 71.065 146.408 1.00 0.00 xxxx 1421 ATOM 1422 CD2 TRP A 182 49.041 70.676 147.049 1.00 0.00 xxxx 1422 ATOM 1423 CE3 TRP A 182 48.840 69.321 147.344 1.00 0.00 xxxx 1423 ATOM 1424 CZ3 TRP A 182 49.825 68.411 146.987 1.00 0.00 xxxx 1424 ATOM 1425 CH2 TRP A 182 51.010 68.831 146.342 1.00 0.00 xxxx 1425 ATOM 1426 CZ2 TRP A 182 51.234 70.149 146.052 1.00 0.00 xxxx 1426 ATOM 1427 C TRP A 182 44.475 71.519 147.973 1.00 0.00 xxxx 1427 ATOM 1428 O TRP A 182 44.418 71.383 149.201 1.00 0.00 xxxx 1428 ATOM 1429 N ASP A 183 43.448 71.898 147.218 1.00 0.00 xxxx 1429 ATOM 1430 CA ASP A 183 42.214 72.426 147.783 1.00 0.00 xxxx 1430 ATOM 1431 CB ASP A 183 41.686 73.566 146.907 1.00 0.00 xxxx 1431 ATOM 1432 CG ASP A 183 40.491 74.259 147.514 1.00 0.00 xxxx 1432 ATOM 1433 OD1 ASP A 183 40.565 74.648 148.697 1.00 0.00 xxxx 1433 ATOM 1434 OD2 ASP A 183 39.463 74.411 146.815 1.00 0.00 xxxx 1434 ATOM 1435 C ASP A 183 41.146 71.348 147.935 1.00 0.00 xxxx 1435 ATOM 1436 O ASP A 183 40.932 70.529 147.039 1.00 0.00 xxxx 1436 ATOM 1437 N ARG A 184 40.477 71.355 149.081 1.00 0.00 xxxx 1437 ATOM 1438 C ARG A 184 38.200 70.639 148.421 1.00 0.00 xxxx 1438 ATOM 1439 O ARG A 184 37.716 69.714 147.782 1.00 0.00 xxxx 1439 ATOM 1440 CA ARG A 184 39.402 70.411 149.347 1.00 0.00 xxxx 1440 ATOM 1441 CB ARG A 184 38.978 70.522 150.818 1.00 0.00 xxxx 1441 ATOM 1442 CG ARG A 184 37.971 69.475 151.277 1.00 0.00 xxxx 1442 ATOM 1443 CD ARG A 184 37.897 69.420 152.808 1.00 0.00 xxxx 1443 ATOM 1444 NE ARG A 184 36.959 68.400 153.274 1.00 0.00 xxxx 1444 ATOM 1445 CZ ARG A 184 36.970 67.868 154.492 1.00 0.00 xxxx 1445 ATOM 1446 NH1 ARG A 184 37.877 68.251 155.382 1.00 0.00 xxxx 1446 ATOM 1447 NH2 ARG A 184 36.070 66.948 154.820 1.00 0.00 xxxx 1447 ATOM 1448 N VAL A 185 37.723 71.878 148.352 1.00 0.00 xxxx 1448 ATOM 1449 CA VAL A 185 36.511 72.147 147.575 1.00 0.00 xxxx 1449 ATOM 1450 CB VAL A 185 35.988 73.561 147.828 1.00 0.00 xxxx 1450 ATOM 1451 CG1 VAL A 185 34.800 73.869 146.907 1.00 0.00 xxxx 1451 ATOM 1452 CG2 VAL A 185 35.568 73.687 149.283 1.00 0.00 xxxx 1452 ATOM 1453 C VAL A 185 36.750 71.902 146.088 1.00 0.00 xxxx 1453 ATOM 1454 O VAL A 185 35.893 71.334 145.400 1.00 0.00 xxxx 1454 ATOM 1455 N THR A 186 37.914 72.300 145.591 1.00 0.00 xxxx 1455 ATOM 1456 CA THR A 186 38.221 72.061 144.181 1.00 0.00 xxxx 1456 ATOM 1457 CB THR A 186 39.561 72.715 143.790 1.00 0.00 xxxx 1457 ATOM 1458 OG1 THR A 186 39.532 74.100 144.155 1.00 0.00 xxxx 1458 ATOM 1459 CG2 THR A 186 39.794 72.603 142.287 1.00 0.00 xxxx 1459 ATOM 1460 C THR A 186 38.258 70.567 143.864 1.00 0.00 xxxx 1460 ATOM 1461 O THR A 186 37.718 70.117 142.852 1.00 0.00 xxxx 1461 ATOM 1462 N ALA A 187 38.887 69.790 144.739 1.00 0.00 xxxx 1462 ATOM 1463 CA ALA A 187 38.937 68.349 144.555 1.00 0.00 xxxx 1463 ATOM 1464 CB ALA A 187 39.807 67.725 145.626 1.00 0.00 xxxx 1464 ATOM 1465 C ALA A 187 37.535 67.743 144.583 1.00 0.00 xxxx 1465 ATOM 1466 O ALA A 187 37.211 66.866 143.789 1.00 0.00 xxxx 1466 ATOM 1467 N HIS A 188 36.712 68.216 145.511 1.00 0.00 xxxx 1467 ATOM 1468 CA HIS A 188 35.322 67.782 145.572 1.00 0.00 xxxx 1468 ATOM 1469 CB HIS A 188 34.566 68.533 146.659 1.00 0.00 xxxx 1469 ATOM 1470 CG HIS A 188 33.084 68.377 146.558 1.00 0.00 xxxx 1470 ATOM 1471 ND1 HIS A 188 32.305 69.204 145.780 1.00 0.00 xxxx 1471 ATOM 1472 CE1 HIS A 188 31.041 68.820 145.871 1.00 0.00 xxxx 1472 ATOM 1473 NE2 HIS A 188 30.981 67.775 146.677 1.00 0.00 xxxx 1473 ATOM 1474 CD2 HIS A 188 32.247 67.473 147.117 1.00 0.00 xxxx 1474 ATOM 1475 C HIS A 188 34.633 67.985 144.232 1.00 0.00 xxxx 1475 ATOM 1476 O HIS A 188 33.967 67.082 143.731 1.00 0.00 xxxx 1476 ATOM 1477 N ASP A 189 34.806 69.170 143.657 1.00 0.00 xxxx 1477 ATOM 1478 CA ASP A 189 34.119 69.515 142.419 1.00 0.00 xxxx 1478 ATOM 1479 CB ASP A 189 34.260 71.012 142.121 1.00 0.00 xxxx 1479 ATOM 1480 CG ASP A 189 33.530 71.898 143.134 1.00 0.00 xxxx 1480 ATOM 1481 OD1 ASP A 189 32.775 71.381 143.997 1.00 0.00 xxxx 1481 ATOM 1482 OD2 ASP A 189 33.715 73.134 143.065 1.00 0.00 xxxx 1482 ATOM 1483 C ASP A 189 34.648 68.674 141.252 1.00 0.00 xxxx 1483 ATOM 1484 O ASP A 189 33.864 68.214 140.414 1.00 0.00 xxxx 1484 ATOM 1485 N LYS A 190 35.966 68.462 141.195 1.00 0.00 xxxx 1485 ATOM 1486 CA LYS A 190 36.543 67.604 140.153 1.00 0.00 xxxx 1486 ATOM 1487 CB LYS A 190 38.076 67.575 140.244 1.00 0.00 xxxx 1487 ATOM 1488 CG LYS A 190 38.773 68.916 140.085 1.00 0.00 xxxx 1488 ATOM 1489 CD LYS A 190 38.692 69.446 138.665 1.00 0.00 xxxx 1489 ATOM 1490 CE LYS A 190 39.552 70.698 138.487 1.00 0.00 xxxx 1490 ATOM 1491 NZ LYS A 190 39.457 71.199 137.081 1.00 0.00 xxxx 1491 ATOM 1492 C LYS A 190 36.000 66.178 140.260 1.00 0.00 xxxx 1492 ATOM 1493 O LYS A 190 35.587 65.570 139.263 1.00 0.00 xxxx 1493 ATOM 1494 N MET A 191 35.997 65.645 141.475 1.00 0.00 xxxx 1494 ATOM 1495 CA MET A 191 35.572 64.268 141.705 1.00 0.00 xxxx 1495 ATOM 1496 CB MET A 191 35.859 63.859 143.152 1.00 0.00 xxxx 1496 ATOM 1497 CG MET A 191 35.582 62.396 143.438 1.00 0.00 xxxx 1497 ATOM 1498 SD MET A 191 36.879 61.354 142.734 1.00 0.00 xxxx 1498 ATOM 1499 CE MET A 191 36.062 59.764 142.708 1.00 0.00 xxxx 1499 ATOM 1500 C MET A 191 34.089 64.078 141.388 1.00 0.00 xxxx 1500 ATOM 1501 O MET A 191 33.701 63.057 140.822 1.00 0.00 xxxx 1501 ATOM 1502 N ALA A 192 33.261 65.061 141.743 1.00 0.00 xxxx 1502 ATOM 1503 CA ALA A 192 31.831 64.962 141.469 1.00 0.00 xxxx 1503 ATOM 1504 CB ALA A 192 31.089 66.163 142.050 1.00 0.00 xxxx 1504 ATOM 1505 C ALA A 192 31.577 64.848 139.966 1.00 0.00 xxxx 1505 ATOM 1506 O ALA A 192 30.724 64.067 139.528 1.00 0.00 xxxx 1506 ATOM 1507 N ALA A 193 32.317 65.628 139.182 1.00 0.00 xxxx 1507 ATOM 1508 CA ALA A 193 32.166 65.611 137.730 1.00 0.00 xxxx 1508 ATOM 1509 CB ALA A 193 32.935 66.779 137.089 1.00 0.00 xxxx 1509 ATOM 1510 C ALA A 193 32.636 64.273 137.159 1.00 0.00 xxxx 1510 ATOM 1511 O ALA A 193 31.990 63.693 136.281 1.00 0.00 xxxx 1511 ATOM 1512 N TRP A 194 33.769 63.781 137.647 1.00 0.00 xxxx 1512 ATOM 1513 CA TRP A 194 34.223 62.454 137.258 1.00 0.00 xxxx 1513 ATOM 1514 CB TRP A 194 35.542 62.121 137.944 1.00 0.00 xxxx 1514 ATOM 1515 CG TRP A 194 36.704 62.930 137.447 1.00 0.00 xxxx 1515 ATOM 1516 CD1 TRP A 194 36.801 63.607 136.258 1.00 0.00 xxxx 1516 ATOM 1517 NE1 TRP A 194 38.028 64.222 136.163 1.00 0.00 xxxx 1517 ATOM 1518 CE2 TRP A 194 38.742 63.957 137.306 1.00 0.00 xxxx 1518 ATOM 1519 CD2 TRP A 194 37.945 63.143 138.128 1.00 0.00 xxxx 1519 ATOM 1520 CE3 TRP A 194 38.448 62.727 139.368 1.00 0.00 xxxx 1520 ATOM 1521 CZ3 TRP A 194 39.729 63.114 139.724 1.00 0.00 xxxx 1521 ATOM 1522 CH2 TRP A 194 40.505 63.930 138.887 1.00 0.00 xxxx 1522 ATOM 1523 CZ2 TRP A 194 40.037 64.356 137.671 1.00 0.00 xxxx 1523 ATOM 1524 C TRP A 194 33.194 61.363 137.577 1.00 0.00 xxxx 1524 ATOM 1525 O TRP A 194 33.000 60.453 136.773 1.00 0.00 xxxx 1525 ATOM 1526 N LEU A 195 32.539 61.445 138.734 1.00 0.00 xxxx 1526 ATOM 1527 CA LEU A 195 31.555 60.419 139.101 1.00 0.00 xxxx 1527 ATOM 1528 CB LEU A 195 31.105 60.591 140.555 1.00 0.00 xxxx 1528 ATOM 1529 CG LEU A 195 32.194 60.179 141.550 1.00 0.00 xxxx 1529 ATOM 1530 CD1 LEU A 195 31.930 60.776 142.929 1.00 0.00 xxxx 1530 ATOM 1531 CD2 LEU A 195 32.294 58.658 141.647 1.00 0.00 xxxx 1531 ATOM 1532 C LEU A 195 30.351 60.446 138.156 1.00 0.00 xxxx 1532 ATOM 1533 O LEU A 195 29.782 59.403 137.827 1.00 0.00 xxxx 1533 ATOM 1534 N SER A 196 29.971 61.638 137.717 1.00 0.00 xxxx 1534 ATOM 1535 CA SER A 196 28.892 61.757 136.749 1.00 0.00 xxxx 1535 ATOM 1536 CB SER A 196 28.511 63.223 136.553 1.00 0.00 xxxx 1536 ATOM 1537 OG SER A 196 27.466 63.342 135.607 1.00 0.00 xxxx 1537 ATOM 1538 C SER A 196 29.292 61.137 135.412 1.00 0.00 xxxx 1538 ATOM 1539 O SER A 196 28.492 60.464 134.759 1.00 0.00 xxxx 1539 ATOM 1540 N SER A 197 30.534 61.370 135.006 1.00 0.00 xxxx 1540 ATOM 1541 CA SER A 197 31.015 60.884 133.710 1.00 0.00 xxxx 1541 ATOM 1542 CB SER A 197 32.301 61.614 133.315 1.00 0.00 xxxx 1542 ATOM 1543 OG SER A 197 32.056 62.978 133.022 1.00 0.00 xxxx 1543 ATOM 1544 C SER A 197 31.278 59.380 133.665 1.00 0.00 xxxx 1544 ATOM 1545 O SER A 197 30.903 58.712 132.700 1.00 0.00 xxxx 1545 ATOM 1546 N PHE A 198 31.933 58.857 134.706 1.00 0.00 xxxx 1546 ATOM 1547 CA PHE A 198 32.506 57.513 134.659 1.00 0.00 xxxx 1547 ATOM 1548 CB PHE A 198 34.024 57.551 134.909 1.00 0.00 xxxx 1548 ATOM 1549 CG PHE A 198 34.792 58.382 133.926 1.00 0.00 xxxx 1549 ATOM 1550 CD1 PHE A 198 34.956 57.953 132.613 1.00 0.00 xxxx 1550 ATOM 1551 CE1 PHE A 198 35.672 58.712 131.702 1.00 0.00 xxxx 1551 ATOM 1552 CZ PHE A 198 36.244 59.908 132.104 1.00 0.00 xxxx 1552 ATOM 1553 CE2 PHE A 198 36.093 60.340 133.413 1.00 0.00 xxxx 1553 ATOM 1554 CD2 PHE A 198 35.374 59.576 134.314 1.00 0.00 xxxx 1554 ATOM 1555 C PHE A 198 31.877 56.591 135.681 1.00 0.00 xxxx 1555 ATOM 1556 O PHE A 198 31.911 55.370 135.529 1.00 0.00 xxxx 1556 ATOM 1557 N GLY A 199 31.334 57.179 136.741 1.00 0.00 xxxx 1557 ATOM 1558 CA GLY A 199 30.585 56.415 137.720 1.00 0.00 xxxx 1558 ATOM 1559 C GLY A 199 31.304 55.216 138.300 1.00 0.00 xxxx 1559 ATOM 1560 O GLY A 199 32.402 55.331 138.867 1.00 0.00 xxxx 1560 ATOM 1561 N ASP A 200 30.704 54.043 138.136 1.00 0.00 xxxx 1561 ATOM 1562 C ASP A 200 32.465 52.304 138.046 1.00 0.00 xxxx 1562 ATOM 1563 O ASP A 200 32.968 51.244 138.394 1.00 0.00 xxxx 1563 ATOM 1564 CA ASP A 200 31.249 52.859 138.788 1.00 0.00 xxxx 1564 ATOM 1565 CB ASP A 200 30.181 51.771 138.933 1.00 0.00 xxxx 1565 ATOM 1566 CG ASP A 200 30.510 50.778 140.040 1.00 0.00 xxxx 1566 ATOM 1567 OD1 ASP A 200 30.918 51.218 141.140 1.00 0.00 xxxx 1567 ATOM 1568 OD2 ASP A 200 30.372 49.560 139.805 1.00 0.00 xxxx 1568 ATOM 1569 N LYS A 201 32.957 53.030 137.045 1.00 0.00 xxxx 1569 ATOM 1570 CA LYS A 201 34.201 52.610 136.394 1.00 0.00 xxxx 1570 ATOM 1571 CB LYS A 201 34.411 53.325 135.062 1.00 0.00 xxxx 1571 ATOM 1572 CG LYS A 201 33.528 52.841 133.934 1.00 0.00 xxxx 1572 ATOM 1573 CD LYS A 201 33.955 53.489 132.626 1.00 0.00 xxxx 1573 ATOM 1574 CE LYS A 201 33.291 52.805 131.449 1.00 0.00 xxxx 1574 ATOM 1575 NZ LYS A 201 33.633 51.346 131.404 1.00 0.00 xxxx 1575 ATOM 1576 C LYS A 201 35.416 52.875 137.282 1.00 0.00 xxxx 1576 ATOM 1577 O LYS A 201 36.447 52.213 137.141 1.00 0.00 xxxx 1577 ATOM 1578 N ILE A 202 35.299 53.852 138.180 1.00 0.00 xxxx 1578 ATOM 1579 CA ILE A 202 36.416 54.249 139.025 1.00 0.00 xxxx 1579 ATOM 1580 CB ILE A 202 36.185 55.625 139.660 1.00 0.00 xxxx 1580 ATOM 1581 CG1 ILE A 202 35.829 56.664 138.591 1.00 0.00 xxxx 1581 ATOM 1582 CD1 ILE A 202 35.524 58.048 139.164 1.00 0.00 xxxx 1582 ATOM 1583 CG2 ILE A 202 37.425 56.056 140.438 1.00 0.00 xxxx 1583 ATOM 1584 C ILE A 202 36.651 53.204 140.107 1.00 0.00 xxxx 1584 ATOM 1585 O ILE A 202 35.737 52.884 140.865 1.00 0.00 xxxx 1585 ATOM 1586 N GLU A 203 37.878 52.694 140.188 1.00 0.00 xxxx 1586 ATOM 1587 CA GLU A 203 38.199 51.627 141.135 1.00 0.00 xxxx 1587 ATOM 1588 CB GLU A 203 38.778 50.417 140.384 1.00 0.00 xxxx 1588 ATOM 1589 CG GLU A 203 37.772 49.792 139.416 1.00 0.00 xxxx 1589 ATOM 1590 CD GLU A 203 38.353 48.684 138.547 1.00 0.00 xxxx 1590 ATOM 1591 OE1 GLU A 203 39.595 48.539 138.479 1.00 0.00 xxxx 1591 ATOM 1592 OE2 GLU A 203 37.561 47.942 137.920 1.00 0.00 xxxx 1592 ATOM 1593 C GLU A 203 39.158 52.075 142.233 1.00 0.00 xxxx 1593 ATOM 1594 O GLU A 203 39.313 51.390 143.245 1.00 0.00 xxxx 1594 ATOM 1595 N ALA A 204 39.778 53.235 142.051 1.00 0.00 xxxx 1595 ATOM 1596 CA ALA A 204 40.764 53.731 143.000 1.00 0.00 xxxx 1596 ATOM 1597 CB ALA A 204 42.099 53.007 142.809 1.00 0.00 xxxx 1597 ATOM 1598 C ALA A 204 40.944 55.236 142.834 1.00 0.00 xxxx 1598 ATOM 1599 O ALA A 204 40.877 55.761 141.720 1.00 0.00 xxxx 1599 ATOM 1600 N VAL A 205 41.167 55.934 143.945 1.00 0.00 xxxx 1600 ATOM 1601 CA VAL A 205 41.404 57.370 143.911 1.00 0.00 xxxx 1601 ATOM 1602 CB VAL A 205 40.278 58.154 144.615 1.00 0.00 xxxx 1602 ATOM 1603 CG1 VAL A 205 40.605 59.641 144.631 1.00 0.00 xxxx 1603 ATOM 1604 CG2 VAL A 205 38.935 57.899 143.941 1.00 0.00 xxxx 1604 ATOM 1605 C VAL A 205 42.724 57.692 144.578 1.00 0.00 xxxx 1605 ATOM 1606 O VAL A 205 42.915 57.366 145.749 1.00 0.00 xxxx 1606 ATOM 1607 N PHE A 206 43.621 58.331 143.835 1.00 0.00 xxxx 1607 ATOM 1608 CA PHE A 206 44.862 58.884 144.392 1.00 0.00 xxxx 1608 ATOM 1609 CB PHE A 206 46.082 58.571 143.509 1.00 0.00 xxxx 1609 ATOM 1610 CG PHE A 206 46.410 57.109 143.392 1.00 0.00 xxxx 1610 ATOM 1611 CD1 PHE A 206 47.402 56.542 144.172 1.00 0.00 xxxx 1611 ATOM 1612 CE1 PHE A 206 47.714 55.194 144.046 1.00 0.00 xxxx 1612 ATOM 1613 CZ PHE A 206 47.034 54.416 143.126 1.00 0.00 xxxx 1613 ATOM 1614 CE2 PHE A 206 46.037 54.971 142.339 1.00 0.00 xxxx 1614 ATOM 1615 CD2 PHE A 206 45.738 56.312 142.466 1.00 0.00 xxxx 1615 ATOM 1616 C PHE A 206 44.733 60.397 144.508 1.00 0.00 xxxx 1616 ATOM 1617 O PHE A 206 44.292 61.053 143.565 1.00 0.00 xxxx 1617 ATOM 1618 N ALA A 207 45.142 60.957 145.645 1.00 0.00 xxxx 1618 ATOM 1619 CA ALA A 207 45.225 62.416 145.769 1.00 0.00 xxxx 1619 ATOM 1620 CB ALA A 207 44.123 62.950 146.678 1.00 0.00 xxxx 1620 ATOM 1621 C ALA A 207 46.594 62.810 146.306 1.00 0.00 xxxx 1621 ATOM 1622 O ALA A 207 47.122 62.146 147.201 1.00 0.00 xxxx 1622 ATOM 1623 N ASN A 208 47.162 63.896 145.787 1.00 0.00 xxxx 1623 ATOM 1624 CA ASN A 208 48.502 64.291 146.219 1.00 0.00 xxxx 1624 ATOM 1625 CB ASN A 208 49.103 65.400 145.344 1.00 0.00 xxxx 1625 ATOM 1626 CG ASN A 208 49.459 64.984 143.909 1.00 0.00 xxxx 1626 ATOM 1627 OD1 ASN A 208 49.763 65.868 143.121 1.00 0.00 xxxx 1627 ATOM 1628 ND2 ASN A 208 49.449 63.689 143.571 1.00 0.00 xxxx 1628 ATOM 1629 C ASN A 208 48.517 64.796 147.679 1.00 0.00 xxxx 1629 ATOM 1630 O ASN A 208 49.590 64.903 148.269 1.00 0.00 xxxx 1630 ATOM 1631 N ASN A 209 47.365 65.153 148.253 1.00 0.00 xxxx 1631 ATOM 1632 CA ASN A 209 47.342 65.466 149.688 1.00 0.00 xxxx 1632 ATOM 1633 CB ASN A 209 47.691 66.955 149.969 1.00 0.00 xxxx 1633 ATOM 1634 CG ASN A 209 46.526 67.920 149.719 1.00 0.00 xxxx 1634 ATOM 1635 OD1 ASN A 209 45.537 67.573 149.075 1.00 0.00 xxxx 1635 ATOM 1636 ND2 ASN A 209 46.667 69.158 150.209 1.00 0.00 xxxx 1636 ATOM 1637 C ASN A 209 46.007 65.097 150.320 1.00 0.00 xxxx 1637 ATOM 1638 O ASN A 209 45.059 64.713 149.633 1.00 0.00 xxxx 1638 ATOM 1639 N ASP A 210 45.958 65.204 151.644 1.00 0.00 xxxx 1639 ATOM 1640 CA ASP A 210 44.773 64.808 152.391 1.00 0.00 xxxx 1640 ATOM 1641 CB ASP A 210 45.055 64.800 153.892 1.00 0.00 xxxx 1641 ATOM 1642 CG ASP A 210 45.798 63.549 154.341 1.00 0.00 xxxx 1642 ATOM 1643 OD1 ASP A 210 46.085 62.662 153.499 1.00 0.00 xxxx 1643 ATOM 1644 OD2 ASP A 210 46.092 63.456 155.547 1.00 0.00 xxxx 1644 ATOM 1645 C ASP A 210 43.581 65.701 152.100 1.00 0.00 xxxx 1645 ATOM 1646 O ASP A 210 42.472 65.208 151.978 1.00 0.00 xxxx 1646 ATOM 1647 N ASP A 211 43.791 67.008 151.985 1.00 0.00 xxxx 1647 ATOM 1648 CA ASP A 211 42.638 67.877 151.766 1.00 0.00 xxxx 1648 ATOM 1649 CB ASP A 211 43.052 69.350 151.760 1.00 0.00 xxxx 1649 ATOM 1650 CG ASP A 211 42.782 70.029 153.091 1.00 0.00 xxxx 1650 ATOM 1651 OD1 ASP A 211 42.301 69.349 154.028 1.00 0.00 xxxx 1651 ATOM 1652 OD2 ASP A 211 43.055 71.240 153.210 1.00 0.00 xxxx 1652 ATOM 1653 C ASP A 211 41.921 67.506 150.469 1.00 0.00 xxxx 1653 ATOM 1654 O ASP A 211 40.698 67.469 150.421 1.00 0.00 xxxx 1654 ATOM 1655 N MET A 212 42.680 67.193 149.427 1.00 0.00 xxxx 1655 ATOM 1656 CA MET A 212 42.048 66.791 148.177 1.00 0.00 xxxx 1656 ATOM 1657 CB MET A 212 43.069 66.817 147.034 1.00 0.00 xxxx 1657 ATOM 1658 CG MET A 212 43.477 68.258 146.686 1.00 0.00 xxxx 1658 ATOM 1659 SD MET A 212 44.495 68.384 145.210 1.00 0.00 xxxx 1659 ATOM 1660 CE MET A 212 45.912 67.363 145.682 1.00 0.00 xxxx 1660 ATOM 1661 C MET A 212 41.397 65.419 148.310 1.00 0.00 xxxx 1661 ATOM 1662 O MET A 212 40.318 65.194 147.763 1.00 0.00 xxxx 1662 ATOM 1663 N ALA A 213 42.031 64.506 149.047 1.00 0.00 xxxx 1663 ATOM 1664 CA ALA A 213 41.423 63.195 149.279 1.00 0.00 xxxx 1664 ATOM 1665 CB ALA A 213 42.346 62.289 150.078 1.00 0.00 xxxx 1665 ATOM 1666 C ALA A 213 40.094 63.354 150.002 1.00 0.00 xxxx 1666 ATOM 1667 O ALA A 213 39.126 62.658 149.683 1.00 0.00 xxxx 1667 ATOM 1668 N LEU A 214 40.048 64.282 150.964 1.00 0.00 xxxx 1668 ATOM 1669 CA LEU A 214 38.842 64.516 151.759 1.00 0.00 xxxx 1669 ATOM 1670 CB LEU A 214 39.158 65.434 152.947 1.00 0.00 xxxx 1670 ATOM 1671 CG LEU A 214 40.111 64.799 153.966 1.00 0.00 xxxx 1671 ATOM 1672 CD1 LEU A 214 40.612 65.821 154.986 1.00 0.00 xxxx 1672 ATOM 1673 CD2 LEU A 214 39.464 63.609 154.670 1.00 0.00 xxxx 1673 ATOM 1674 C LEU A 214 37.717 65.104 150.922 1.00 0.00 xxxx 1674 ATOM 1675 O LEU A 214 36.555 64.746 151.102 1.00 0.00 xxxx 1675 ATOM 1676 N GLY A 215 38.066 66.001 150.004 1.00 0.00 xxxx 1676 ATOM 1677 CA GLY A 215 37.088 66.537 149.067 1.00 0.00 xxxx 1677 ATOM 1678 C GLY A 215 36.551 65.438 148.168 1.00 0.00 xxxx 1678 ATOM 1679 O GLY A 215 35.345 65.377 147.911 1.00 0.00 xxxx 1679 ATOM 1680 N ALA A 216 37.442 64.573 147.688 1.00 0.00 xxxx 1680 ATOM 1681 CA ALA A 216 37.020 63.429 146.885 1.00 0.00 xxxx 1681 ATOM 1682 CB ALA A 216 38.230 62.655 146.374 1.00 0.00 xxxx 1682 ATOM 1683 C ALA A 216 36.090 62.516 147.688 1.00 0.00 xxxx 1683 ATOM 1684 O ALA A 216 35.066 62.062 147.170 1.00 0.00 xxxx 1684 ATOM 1685 N ILE A 217 36.424 62.270 148.952 1.00 0.00 xxxx 1685 ATOM 1686 CA ILE A 217 35.583 61.438 149.805 1.00 0.00 xxxx 1686 ATOM 1687 CB ILE A 217 36.275 61.186 151.167 1.00 0.00 xxxx 1687 ATOM 1688 CG1 ILE A 217 37.406 60.171 150.988 1.00 0.00 xxxx 1688 ATOM 1689 CD1 ILE A 217 38.425 60.184 152.118 1.00 0.00 xxxx 1689 ATOM 1690 CG2 ILE A 217 35.265 60.695 152.221 1.00 0.00 xxxx 1690 ATOM 1691 C ILE A 217 34.187 62.049 149.971 1.00 0.00 xxxx 1691 ATOM 1692 O ILE A 217 33.188 61.327 149.967 1.00 0.00 xxxx 1692 ATOM 1693 N GLU A 218 34.089 63.371 150.075 1.00 0.00 xxxx 1693 ATOM 1694 C GLU A 218 31.948 63.832 148.945 1.00 0.00 xxxx 1694 ATOM 1695 O GLU A 218 30.736 63.621 149.019 1.00 0.00 xxxx 1695 ATOM 1696 CA GLU A 218 32.781 64.001 150.218 1.00 0.00 xxxx 1696 ATOM 1697 CB GLU A 218 32.925 65.482 150.574 1.00 0.00 xxxx 1697 ATOM 1698 CG GLU A 218 33.457 65.727 151.983 1.00 0.00 xxxx 1698 ATOM 1699 CD GLU A 218 32.729 64.911 153.046 1.00 0.00 xxxx 1699 ATOM 1700 OE1 GLU A 218 31.482 64.948 153.089 1.00 0.00 xxxx 1700 ATOM 1701 OE2 GLU A 218 33.401 64.221 153.840 1.00 0.00 xxxx 1701 ATOM 1702 N ALA A 219 32.593 63.921 147.783 1.00 0.00 xxxx 1702 ATOM 1703 CA ALA A 219 31.881 63.696 146.531 1.00 0.00 xxxx 1703 ATOM 1704 CB ALA A 219 32.763 64.063 145.327 1.00 0.00 xxxx 1704 ATOM 1705 C ALA A 219 31.431 62.237 146.444 1.00 0.00 xxxx 1705 ATOM 1706 O ALA A 219 30.321 61.945 145.997 1.00 0.00 xxxx 1706 ATOM 1707 N LEU A 220 32.294 61.329 146.890 1.00 0.00 xxxx 1707 ATOM 1708 CA LEU A 220 31.957 59.907 146.898 1.00 0.00 xxxx 1708 ATOM 1709 CB LEU A 220 33.175 59.083 147.291 1.00 0.00 xxxx 1709 ATOM 1710 CG LEU A 220 34.251 59.007 146.209 1.00 0.00 xxxx 1710 ATOM 1711 CD1 LEU A 220 35.601 58.672 146.812 1.00 0.00 xxxx 1711 ATOM 1712 CD2 LEU A 220 33.837 57.986 145.144 1.00 0.00 xxxx 1712 ATOM 1713 C LEU A 220 30.793 59.605 147.836 1.00 0.00 xxxx 1713 ATOM 1714 O LEU A 220 29.876 58.868 147.475 1.00 0.00 xxxx 1714 ATOM 1715 N LYS A 221 30.824 60.164 149.045 1.00 0.00 xxxx 1715 ATOM 1716 CA LYS A 221 29.687 60.015 149.962 1.00 0.00 xxxx 1716 ATOM 1717 CB LYS A 221 29.930 60.789 151.258 1.00 0.00 xxxx 1717 ATOM 1718 CG LYS A 221 30.943 60.170 152.186 1.00 0.00 xxxx 1718 ATOM 1719 CD LYS A 221 31.170 61.087 153.369 1.00 0.00 xxxx 1719 ATOM 1720 CE LYS A 221 32.082 60.452 154.396 1.00 0.00 xxxx 1720 ATOM 1721 NZ LYS A 221 32.368 61.404 155.504 1.00 0.00 xxxx 1721 ATOM 1722 C LYS A 221 28.379 60.492 149.320 1.00 0.00 xxxx 1722 ATOM 1723 O LYS A 221 27.353 59.801 149.365 1.00 0.00 xxxx 1723 ATOM 1724 N SER A 222 28.431 61.671 148.709 1.00 0.00 xxxx 1724 ATOM 1725 CA SER A 222 27.258 62.263 148.063 1.00 0.00 xxxx 1725 ATOM 1726 CB SER A 222 27.626 63.620 147.450 1.00 0.00 xxxx 1726 ATOM 1727 OG SER A 222 26.484 64.308 146.967 1.00 0.00 xxxx 1727 ATOM 1728 C SER A 222 26.670 61.340 146.992 1.00 0.00 xxxx 1728 ATOM 1729 O SER A 222 25.451 61.321 146.773 1.00 0.00 xxxx 1729 ATOM 1730 N ALA A 223 27.539 60.569 146.346 1.00 0.00 xxxx 1730 ATOM 1731 CA ALA A 223 27.144 59.633 145.295 1.00 0.00 xxxx 1731 ATOM 1732 CB ALA A 223 28.227 59.565 144.226 1.00 0.00 xxxx 1732 ATOM 1733 C ALA A 223 26.844 58.224 145.823 1.00 0.00 xxxx 1733 ATOM 1734 O ALA A 223 26.640 57.299 145.039 1.00 0.00 xxxx 1734 ATOM 1735 N GLY A 224 26.837 58.055 147.143 1.00 0.00 xxxx 1735 ATOM 1736 CA GLY A 224 26.391 56.803 147.737 1.00 0.00 xxxx 1736 ATOM 1737 C GLY A 224 27.439 55.849 148.286 1.00 0.00 xxxx 1737 ATOM 1738 O GLY A 224 27.099 54.754 148.749 1.00 0.00 xxxx 1738 ATOM 1739 N TYR A 225 28.705 56.254 148.247 1.00 0.00 xxxx 1739 ATOM 1740 CA TYR A 225 29.790 55.423 148.772 1.00 0.00 xxxx 1740 ATOM 1741 CB TYR A 225 31.126 55.823 148.132 1.00 0.00 xxxx 1741 ATOM 1742 CG TYR A 225 31.231 55.438 146.673 1.00 0.00 xxxx 1742 ATOM 1743 CD1 TYR A 225 30.582 56.178 145.691 1.00 0.00 xxxx 1743 ATOM 1744 CE1 TYR A 225 30.666 55.826 144.354 1.00 0.00 xxxx 1744 ATOM 1745 CZ TYR A 225 31.403 54.721 143.983 1.00 0.00 xxxx 1745 ATOM 1746 OH TYR A 225 31.483 54.376 142.652 1.00 0.00 xxxx 1746 ATOM 1747 CE2 TYR A 225 32.056 53.963 144.937 1.00 0.00 xxxx 1747 ATOM 1748 CD2 TYR A 225 31.963 54.321 146.276 1.00 0.00 xxxx 1748 ATOM 1749 C TYR A 225 29.901 55.507 150.290 1.00 0.00 xxxx 1749 ATOM 1750 O TYR A 225 29.427 56.464 150.907 1.00 0.00 xxxx 1750 ATOM 1751 N PHE A 226 30.514 54.479 150.874 1.00 0.00 xxxx 1751 ATOM 1752 CA PHE A 226 30.855 54.433 152.295 1.00 0.00 xxxx 1752 ATOM 1753 CB PHE A 226 31.676 55.662 152.679 1.00 0.00 xxxx 1753 ATOM 1754 CG PHE A 226 32.925 55.809 151.866 1.00 0.00 xxxx 1754 ATOM 1755 CD1 PHE A 226 33.835 54.764 151.787 1.00 0.00 xxxx 1755 ATOM 1756 CE1 PHE A 226 34.990 54.881 151.019 1.00 0.00 xxxx 1756 ATOM 1757 CZ PHE A 226 35.233 56.055 150.313 1.00 0.00 xxxx 1757 ATOM 1758 CE2 PHE A 226 34.318 57.101 150.383 1.00 0.00 xxxx 1758 ATOM 1759 CD2 PHE A 226 33.174 56.972 151.150 1.00 0.00 xxxx 1759 ATOM 1760 C PHE A 226 29.627 54.297 153.184 1.00 0.00 xxxx 1760 ATOM 1761 O PHE A 226 29.662 54.619 154.369 1.00 0.00 xxxx 1761 ATOM 1762 N THR A 227 28.547 53.815 152.583 1.00 0.00 xxxx 1762 ATOM 1763 CA THR A 227 27.374 53.347 153.311 1.00 0.00 xxxx 1763 ATOM 1764 CB THR A 227 26.239 54.382 153.335 1.00 0.00 xxxx 1764 ATOM 1765 OG1 THR A 227 25.133 53.854 154.076 1.00 0.00 xxxx 1765 ATOM 1766 CG2 THR A 227 25.785 54.714 151.924 1.00 0.00 xxxx 1766 ATOM 1767 C THR A 227 26.930 52.070 152.610 1.00 0.00 xxxx 1767 ATOM 1768 O THR A 227 27.137 51.920 151.405 1.00 0.00 xxxx 1768 ATOM 1769 N GLY A 228 26.331 51.145 153.349 1.00 0.00 xxxx 1769 ATOM 1770 CA GLY A 228 26.122 49.818 152.804 1.00 0.00 xxxx 1770 ATOM 1771 C GLY A 228 27.484 49.199 152.547 1.00 0.00 xxxx 1771 ATOM 1772 O GLY A 228 28.433 49.473 153.281 1.00 0.00 xxxx 1772 ATOM 1773 N ASN A 229 27.601 48.384 151.505 1.00 0.00 xxxx 1773 ATOM 1774 CA ASN A 229 28.884 47.756 151.200 1.00 0.00 xxxx 1774 ATOM 1775 CB ASN A 229 28.697 46.259 150.932 1.00 0.00 xxxx 1775 ATOM 1776 CG ASN A 229 27.629 45.977 149.888 1.00 0.00 xxxx 1776 ATOM 1777 OD1 ASN A 229 27.160 46.885 149.199 1.00 0.00 xxxx 1777 ATOM 1778 ND2 ASN A 229 27.241 44.711 149.766 1.00 0.00 xxxx 1778 ATOM 1779 C ASN A 229 29.591 48.414 150.013 1.00 0.00 xxxx 1779 ATOM 1780 O ASN A 229 30.509 47.831 149.435 1.00 0.00 xxxx 1780 ATOM 1781 N LYS A 230 29.165 49.627 149.661 1.00 0.00 xxxx 1781 ATOM 1782 CA LYS A 230 29.696 50.331 148.491 1.00 0.00 xxxx 1782 ATOM 1783 CB LYS A 230 28.645 51.284 147.926 1.00 0.00 xxxx 1783 ATOM 1784 CG LYS A 230 29.049 51.957 146.625 1.00 0.00 xxxx 1784 ATOM 1785 CD LYS A 230 27.920 52.840 146.108 1.00 0.00 xxxx 1785 ATOM 1786 CE LYS A 230 28.136 53.249 144.662 1.00 0.00 xxxx 1786 ATOM 1787 NZ LYS A 230 27.043 54.140 144.184 1.00 0.00 xxxx 1787 ATOM 1788 C LYS A 230 30.975 51.104 148.820 1.00 0.00 xxxx 1788 ATOM 1789 O LYS A 230 30.931 52.156 149.455 1.00 0.00 xxxx 1789 ATOM 1790 N TYR A 231 32.107 50.592 148.352 1.00 0.00 xxxx 1790 ATOM 1791 CA TYR A 231 33.403 51.068 148.820 1.00 0.00 xxxx 1791 ATOM 1792 CB TYR A 231 34.020 50.021 149.742 1.00 0.00 xxxx 1792 ATOM 1793 CG TYR A 231 35.396 50.366 150.248 1.00 0.00 xxxx 1793 ATOM 1794 CD1 TYR A 231 35.558 51.179 151.358 1.00 0.00 xxxx 1794 ATOM 1795 CE1 TYR A 231 36.809 51.500 151.828 1.00 0.00 xxxx 1795 ATOM 1796 CZ TYR A 231 37.927 50.995 151.187 1.00 0.00 xxxx 1796 ATOM 1797 OH TYR A 231 39.183 51.307 151.656 1.00 0.00 xxxx 1797 ATOM 1798 CE2 TYR A 231 37.790 50.178 150.084 1.00 0.00 xxxx 1798 ATOM 1799 CD2 TYR A 231 36.533 49.867 149.624 1.00 0.00 xxxx 1799 ATOM 1800 C TYR A 231 34.359 51.383 147.680 1.00 0.00 xxxx 1800 ATOM 1801 O TYR A 231 34.282 50.778 146.616 1.00 0.00 xxxx 1801 ATOM 1802 N ILE A 232 35.259 52.334 147.914 1.00 0.00 xxxx 1802 ATOM 1803 CA ILE A 232 36.330 52.633 146.976 1.00 0.00 xxxx 1803 ATOM 1804 CB ILE A 232 35.913 53.708 145.951 1.00 0.00 xxxx 1804 ATOM 1805 CG1 ILE A 232 37.027 53.945 144.941 1.00 0.00 xxxx 1805 ATOM 1806 CD1 ILE A 232 36.591 54.744 143.743 1.00 0.00 xxxx 1806 ATOM 1807 CG2 ILE A 232 35.555 55.020 146.649 1.00 0.00 xxxx 1807 ATOM 1808 C ILE A 232 37.548 53.063 147.793 1.00 0.00 xxxx 1808 ATOM 1809 O ILE A 232 37.413 53.817 148.754 1.00 0.00 xxxx 1809 ATOM 1810 N PRO A 233 38.739 52.558 147.441 1.00 0.00 xxxx 1810 ATOM 1811 CA PRO A 233 39.939 52.965 148.184 1.00 0.00 xxxx 1811 ATOM 1812 CB PRO A 233 40.955 51.880 147.820 1.00 0.00 xxxx 1812 ATOM 1813 CG PRO A 233 40.537 51.453 146.432 1.00 0.00 xxxx 1813 ATOM 1814 CD PRO A 233 39.026 51.487 146.470 1.00 0.00 xxxx 1814 ATOM 1815 C PRO A 233 40.438 54.344 147.769 1.00 0.00 xxxx 1815 ATOM 1816 O PRO A 233 40.593 54.627 146.578 1.00 0.00 xxxx 1816 ATOM 1817 N VAL A 234 40.678 55.196 148.762 1.00 0.00 xxxx 1817 ATOM 1818 CA VAL A 234 41.174 56.546 148.544 1.00 0.00 xxxx 1818 ATOM 1819 CB VAL A 234 40.142 57.602 148.976 1.00 0.00 xxxx 1819 ATOM 1820 CG1 VAL A 234 40.678 58.996 148.715 1.00 0.00 xxxx 1820 ATOM 1821 CG2 VAL A 234 38.804 57.384 148.267 1.00 0.00 xxxx 1821 ATOM 1822 C VAL A 234 42.452 56.709 149.345 1.00 0.00 xxxx 1822 ATOM 1823 O VAL A 234 42.484 56.346 150.522 1.00 0.00 xxxx 1823 ATOM 1824 N VAL A 235 43.501 57.258 148.732 1.00 0.00 xxxx 1824 ATOM 1825 CA VAL A 235 44.757 57.491 149.447 1.00 0.00 xxxx 1825 ATOM 1826 CB VAL A 235 45.869 56.539 148.964 1.00 0.00 xxxx 1826 ATOM 1827 CG1 VAL A 235 45.519 55.097 149.324 1.00 0.00 xxxx 1827 ATOM 1828 CG2 VAL A 235 46.099 56.699 147.468 1.00 0.00 xxxx 1828 ATOM 1829 C VAL A 235 45.189 58.952 149.316 1.00 0.00 xxxx 1829 ATOM 1830 O VAL A 235 44.972 59.583 148.280 1.00 0.00 xxxx 1830 ATOM 1831 N GLY A 236 45.764 59.496 150.387 1.00 0.00 xxxx 1831 ATOM 1832 CA GLY A 236 46.282 60.856 150.371 1.00 0.00 xxxx 1832 ATOM 1833 C GLY A 236 47.705 60.961 150.892 1.00 0.00 xxxx 1833 ATOM 1834 O GLY A 236 48.418 59.958 150.963 1.00 0.00 xxxx 1834 ATOM 1835 N VAL A 237 48.119 62.185 151.231 1.00 0.00 xxxx 1835 ATOM 1836 CA VAL A 237 49.399 62.461 151.893 1.00 0.00 xxxx 1836 ATOM 1837 CB VAL A 237 50.527 62.876 150.914 1.00 0.00 xxxx 1837 ATOM 1838 CG1 VAL A 237 51.746 63.309 151.700 1.00 0.00 xxxx 1838 ATOM 1839 CG2 VAL A 237 50.896 61.745 149.967 1.00 0.00 xxxx 1839 ATOM 1840 C VAL A 237 49.189 63.600 152.885 1.00 0.00 xxxx 1840 ATOM 1841 O VAL A 237 48.552 64.589 152.520 1.00 0.00 xxxx 1841 ATOM 1842 N ASP A 238 49.692 63.425 154.113 1.00 0.00 xxxx 1842 ATOM 1843 CA ASP A 238 49.966 64.468 155.127 1.00 0.00 xxxx 1843 ATOM 1844 CB ASP A 238 49.128 65.746 154.971 1.00 0.00 xxxx 1844 ATOM 1845 CG ASP A 238 49.636 66.668 153.871 1.00 0.00 xxxx 1845 ATOM 1846 OD1 ASP A 238 50.792 66.524 153.414 1.00 0.00 xxxx 1846 ATOM 1847 OD2 ASP A 238 48.841 67.527 153.432 1.00 0.00 xxxx 1847 ATOM 1848 C ASP A 238 49.713 63.921 156.526 1.00 0.00 xxxx 1848 ATOM 1849 O ASP A 238 50.480 64.184 157.447 1.00 0.00 xxxx 1849 ATOM 1850 N ALA A 239 48.611 63.191 156.679 1.00 0.00 xxxx 1850 ATOM 1851 CA ALA A 239 48.125 62.740 157.989 1.00 0.00 xxxx 1851 ATOM 1852 CB ALA A 239 49.145 61.812 158.674 1.00 0.00 xxxx 1852 ATOM 1853 C ALA A 239 47.783 63.936 158.881 1.00 0.00 xxxx 1853 ATOM 1854 O ALA A 239 48.171 64.008 160.055 1.00 0.00 xxxx 1854 ATOM 1855 N THR A 240 47.049 64.883 158.301 1.00 0.00 xxxx 1855 ATOM 1856 CA THR A 240 46.483 65.989 159.060 1.00 0.00 xxxx 1856 ATOM 1857 CB THR A 240 45.850 67.040 158.148 1.00 0.00 xxxx 1857 ATOM 1858 OG1 THR A 240 44.789 66.424 157.409 1.00 0.00 xxxx 1858 ATOM 1859 CG2 THR A 240 46.883 67.627 157.184 1.00 0.00 xxxx 1859 ATOM 1860 C THR A 240 45.408 65.453 159.994 1.00 0.00 xxxx 1860 ATOM 1861 O THR A 240 45.001 64.297 159.883 1.00 0.00 xxxx 1861 ATOM 1862 N ALA A 241 44.948 66.295 160.914 1.00 0.00 xxxx 1862 ATOM 1863 CA ALA A 241 43.896 65.887 161.837 1.00 0.00 xxxx 1863 ATOM 1864 CB ALA A 241 43.531 67.044 162.781 1.00 0.00 xxxx 1864 ATOM 1865 C ALA A 241 42.648 65.357 161.094 1.00 0.00 xxxx 1865 ATOM 1866 O ALA A 241 42.175 64.264 161.408 1.00 0.00 xxxx 1866 ATOM 1867 N PRO A 242 42.131 66.098 160.089 1.00 0.00 xxxx 1867 ATOM 1868 CA PRO A 242 40.978 65.500 159.401 1.00 0.00 xxxx 1868 ATOM 1869 CB PRO A 242 40.446 66.648 158.532 1.00 0.00 xxxx 1869 ATOM 1870 CG PRO A 242 41.594 67.555 158.345 1.00 0.00 xxxx 1870 ATOM 1871 CD PRO A 242 42.406 67.464 159.607 1.00 0.00 xxxx 1871 ATOM 1872 C PRO A 242 41.340 64.283 158.544 1.00 0.00 xxxx 1872 ATOM 1873 O PRO A 242 40.493 63.415 158.346 1.00 0.00 xxxx 1873 ATOM 1874 N GLY A 243 42.577 64.202 158.063 1.00 0.00 xxxx 1874 ATOM 1875 CA GLY A 243 43.011 62.995 157.379 1.00 0.00 xxxx 1875 ATOM 1876 C GLY A 243 42.969 61.786 158.305 1.00 0.00 xxxx 1876 ATOM 1877 O GLY A 243 42.437 60.724 157.961 1.00 0.00 xxxx 1877 ATOM 1878 N ILE A 244 43.533 61.955 159.499 1.00 0.00 xxxx 1878 ATOM 1879 CA ILE A 244 43.549 60.895 160.500 1.00 0.00 xxxx 1879 ATOM 1880 CB ILE A 244 44.333 61.342 161.748 1.00 0.00 xxxx 1880 ATOM 1881 CG1 ILE A 244 45.826 61.443 161.425 1.00 0.00 xxxx 1881 ATOM 1882 CD1 ILE A 244 46.597 62.226 162.456 1.00 0.00 xxxx 1882 ATOM 1883 CG2 ILE A 244 44.076 60.408 162.929 1.00 0.00 xxxx 1883 ATOM 1884 C ILE A 244 42.120 60.491 160.841 1.00 0.00 xxxx 1884 ATOM 1885 O ILE A 244 41.808 59.306 160.941 1.00 0.00 xxxx 1885 ATOM 1886 N GLN A 245 41.241 61.475 160.982 1.00 0.00 xxxx 1886 ATOM 1887 CA GLN A 245 39.851 61.177 161.287 1.00 0.00 xxxx 1887 ATOM 1888 CB GLN A 245 39.063 62.469 161.501 1.00 0.00 xxxx 1888 ATOM 1889 CG GLN A 245 37.649 62.224 161.982 1.00 0.00 xxxx 1889 ATOM 1890 CD GLN A 245 37.621 61.498 163.314 1.00 0.00 xxxx 1890 ATOM 1891 OE1 GLN A 245 38.162 61.987 164.309 1.00 0.00 xxxx 1891 ATOM 1892 NE2 GLN A 245 37.011 60.315 163.335 1.00 0.00 xxxx 1892 ATOM 1893 C GLN A 245 39.192 60.328 160.189 1.00 0.00 xxxx 1893 ATOM 1894 O GLN A 245 38.414 59.418 160.494 1.00 0.00 xxxx 1894 ATOM 1895 N ALA A 246 39.521 60.598 158.924 1.00 0.00 xxxx 1895 ATOM 1896 CA ALA A 246 38.941 59.829 157.819 1.00 0.00 xxxx 1896 ATOM 1897 CB ALA A 246 39.202 60.523 156.490 1.00 0.00 xxxx 1897 ATOM 1898 C ALA A 246 39.478 58.396 157.783 1.00 0.00 xxxx 1898 ATOM 1899 O ALA A 246 38.764 57.472 157.390 1.00 0.00 xxxx 1899 ATOM 1900 N ILE A 247 40.734 58.206 158.193 1.00 0.00 xxxx 1900 ATOM 1901 CA ILE A 247 41.272 56.854 158.343 1.00 0.00 xxxx 1901 ATOM 1902 CB ILE A 247 42.765 56.866 158.712 1.00 0.00 xxxx 1902 ATOM 1903 CG1 ILE A 247 43.583 57.467 157.566 1.00 0.00 xxxx 1903 ATOM 1904 CD1 ILE A 247 45.054 57.286 157.705 1.00 0.00 xxxx 1904 ATOM 1905 CG2 ILE A 247 43.249 55.456 159.063 1.00 0.00 xxxx 1905 ATOM 1906 C ILE A 247 40.469 56.101 159.392 1.00 0.00 xxxx 1906 ATOM 1907 O ILE A 247 40.092 54.951 159.199 1.00 0.00 xxxx 1907 ATOM 1908 N LYS A 248 40.209 56.767 160.509 1.00 0.00 xxxx 1908 ATOM 1909 CA LYS A 248 39.428 56.166 161.578 1.00 0.00 xxxx 1909 ATOM 1910 CB LYS A 248 39.441 57.071 162.803 1.00 0.00 xxxx 1910 ATOM 1911 CG LYS A 248 40.813 57.187 163.463 1.00 0.00 xxxx 1911 ATOM 1912 CD LYS A 248 40.756 58.156 164.623 1.00 0.00 xxxx 1912 ATOM 1913 CE LYS A 248 42.102 58.310 165.291 1.00 0.00 xxxx 1913 ATOM 1914 NZ LYS A 248 42.032 59.317 166.388 1.00 0.00 xxxx 1914 ATOM 1915 C LYS A 248 37.988 55.882 161.142 1.00 0.00 xxxx 1915 ATOM 1916 O LYS A 248 37.416 54.866 161.539 1.00 0.00 xxxx 1916 ATOM 1917 N ASP A 249 37.424 56.776 160.329 1.00 0.00 xxxx 1917 ATOM 1918 CA ASP A 249 36.057 56.640 159.803 1.00 0.00 xxxx 1918 ATOM 1919 CB ASP A 249 35.598 57.937 159.114 1.00 0.00 xxxx 1919 ATOM 1920 CG ASP A 249 35.429 59.101 160.078 1.00 0.00 xxxx 1920 ATOM 1921 OD1 ASP A 249 35.413 60.260 159.603 1.00 0.00 xxxx 1921 ATOM 1922 OD2 ASP A 249 35.308 58.871 161.301 1.00 0.00 xxxx 1922 ATOM 1923 C ASP A 249 35.949 55.489 158.798 1.00 0.00 xxxx 1923 ATOM 1924 O ASP A 249 34.853 55.002 158.507 1.00 0.00 xxxx 1924 ATOM 1925 N GLY A 250 37.091 55.085 158.251 1.00 0.00 xxxx 1925 ATOM 1926 CA GLY A 250 37.138 54.047 157.237 1.00 0.00 xxxx 1926 ATOM 1927 C GLY A 250 36.984 54.551 155.809 1.00 0.00 xxxx 1927 ATOM 1928 O GLY A 250 36.947 53.755 154.876 1.00 0.00 xxxx 1928 ATOM 1929 N THR A 251 36.900 55.868 155.636 1.00 0.00 xxxx 1929 ATOM 1930 CA THR A 251 36.671 56.458 154.313 1.00 0.00 xxxx 1930 ATOM 1931 CB THR A 251 35.837 57.756 154.403 1.00 0.00 xxxx 1931 ATOM 1932 OG1 THR A 251 36.531 58.731 155.198 1.00 0.00 xxxx 1932 ATOM 1933 CG2 THR A 251 34.449 57.472 154.995 1.00 0.00 xxxx 1933 ATOM 1934 C THR A 251 37.972 56.777 153.566 1.00 0.00 xxxx 1934 ATOM 1935 O THR A 251 37.973 56.923 152.346 1.00 0.00 xxxx 1935 ATOM 1936 N LEU A 252 39.070 56.900 154.306 1.00 0.00 xxxx 1936 ATOM 1937 CA LEU A 252 40.393 57.080 153.715 1.00 0.00 xxxx 1937 ATOM 1938 CB LEU A 252 41.089 58.317 154.297 1.00 0.00 xxxx 1938 ATOM 1939 CG LEU A 252 42.427 58.752 153.692 1.00 0.00 xxxx 1939 ATOM 1940 CD1 LEU A 252 42.273 59.128 152.211 1.00 0.00 xxxx 1940 ATOM 1941 CD2 LEU A 252 43.008 59.929 154.472 1.00 0.00 xxxx 1941 ATOM 1942 C LEU A 252 41.195 55.812 153.989 1.00 0.00 xxxx 1942 ATOM 1943 O LEU A 252 41.347 55.412 155.139 1.00 0.00 xxxx 1943 ATOM 1944 N LEU A 253 41.685 55.169 152.934 1.00 0.00 xxxx 1944 ATOM 1945 CA LEU A 253 42.397 53.903 153.086 1.00 0.00 xxxx 1945 ATOM 1946 CB LEU A 253 42.601 53.240 151.717 1.00 0.00 xxxx 1946 ATOM 1947 CG LEU A 253 43.518 52.011 151.707 1.00 0.00 xxxx 1947 ATOM 1948 CD1 LEU A 253 42.917 50.848 152.514 1.00 0.00 xxxx 1948 ATOM 1949 CD2 LEU A 253 43.811 51.593 150.278 1.00 0.00 xxxx 1949 ATOM 1950 C LEU A 253 43.742 54.105 153.776 1.00 0.00 xxxx 1950 ATOM 1951 O LEU A 253 44.149 53.333 154.648 1.00 0.00 xxxx 1951 ATOM 1952 N GLY A 254 44.441 55.157 153.389 1.00 0.00 xxxx 1952 ATOM 1953 CA GLY A 254 45.749 55.381 153.958 1.00 0.00 xxxx 1953 ATOM 1954 C GLY A 254 46.259 56.739 153.579 1.00 0.00 xxxx 1954 ATOM 1955 O GLY A 254 45.695 57.409 152.710 1.00 0.00 xxxx 1955 ATOM 1956 N THR A 255 47.328 57.144 154.249 1.00 0.00 xxxx 1956 ATOM 1957 CA THR A 255 47.980 58.395 153.941 1.00 0.00 xxxx 1957 ATOM 1958 CB THR A 255 47.293 59.602 154.650 1.00 0.00 xxxx 1958 ATOM 1959 OG1 THR A 255 47.875 60.829 154.206 1.00 0.00 xxxx 1959 ATOM 1960 CG2 THR A 255 47.392 59.517 156.170 1.00 0.00 xxxx 1960 ATOM 1961 C THR A 255 49.445 58.255 154.340 1.00 0.00 xxxx 1961 ATOM 1962 O THR A 255 49.913 57.156 154.636 1.00 0.00 xxxx 1962 ATOM 1963 N VAL A 256 50.169 59.363 154.283 1.00 0.00 xxxx 1963 ATOM 1964 CA VAL A 256 51.593 59.376 154.584 1.00 0.00 xxxx 1964 ATOM 1965 CB VAL A 256 52.434 59.484 153.297 1.00 0.00 xxxx 1965 ATOM 1966 CG1 VAL A 256 53.924 59.449 153.622 1.00 0.00 xxxx 1966 ATOM 1967 CG2 VAL A 256 52.054 58.386 152.302 1.00 0.00 xxxx 1967 ATOM 1968 C VAL A 256 51.827 60.559 155.495 1.00 0.00 xxxx 1968 ATOM 1969 O VAL A 256 51.471 61.677 155.149 1.00 0.00 xxxx 1969 ATOM 1970 N LEU A 257 52.399 60.316 156.668 1.00 0.00 xxxx 1970 ATOM 1971 CA LEU A 257 52.679 61.405 157.585 1.00 0.00 xxxx 1971 ATOM 1972 CB LEU A 257 53.143 60.875 158.938 1.00 0.00 xxxx 1972 ATOM 1973 CG LEU A 257 53.668 61.969 159.872 1.00 0.00 xxxx 1973 ATOM 1974 CD1 LEU A 257 52.555 62.938 160.270 1.00 0.00 xxxx 1974 ATOM 1975 CD2 LEU A 257 54.331 61.346 161.102 1.00 0.00 xxxx 1975 ATOM 1976 C LEU A 257 53.734 62.335 157.011 1.00 0.00 xxxx 1976 ATOM 1977 O LEU A 257 54.852 61.915 156.704 1.00 0.00 xxxx 1977 ATOM 1978 N ASN A 258 53.348 63.593 156.841 1.00 0.00 xxxx 1978 ATOM 1979 CA ASN A 258 54.252 64.663 156.459 1.00 0.00 xxxx 1979 ATOM 1980 CB ASN A 258 53.592 65.620 155.458 1.00 0.00 xxxx 1980 ATOM 1981 CG ASN A 258 54.584 66.574 154.797 1.00 0.00 xxxx 1981 ATOM 1982 OD1 ASN A 258 55.805 66.410 154.900 1.00 0.00 xxxx 1982 ATOM 1983 ND2 ASN A 258 54.054 67.560 154.084 1.00 0.00 xxxx 1983 ATOM 1984 C ASN A 258 54.577 65.344 157.771 1.00 0.00 xxxx 1984 ATOM 1985 O ASN A 258 53.705 65.942 158.400 1.00 0.00 xxxx 1985 ATOM 1986 N ASP A 259 55.822 65.207 158.207 1.00 0.00 xxxx 1986 ATOM 1987 CA ASP A 259 56.197 65.545 159.576 1.00 0.00 xxxx 1987 ATOM 1988 CB ASP A 259 57.455 64.762 159.955 1.00 0.00 xxxx 1988 ATOM 1989 CG ASP A 259 57.789 64.844 161.431 1.00 0.00 xxxx 1989 ATOM 1990 OD1 ASP A 259 57.216 65.690 162.151 1.00 0.00 xxxx 1990 ATOM 1991 OD2 ASP A 259 58.660 64.056 161.860 1.00 0.00 xxxx 1991 ATOM 1992 C ASP A 259 56.415 67.048 159.739 1.00 0.00 xxxx 1992 ATOM 1993 O ASP A 259 57.549 67.531 159.710 1.00 0.00 xxxx 1993 ATOM 1994 N ALA A 260 55.314 67.772 159.923 1.00 0.00 xxxx 1994 ATOM 1995 CA ALA A 260 55.334 69.218 160.026 1.00 0.00 xxxx 1995 ATOM 1996 CB ALA A 260 53.903 69.762 160.105 1.00 0.00 xxxx 1996 ATOM 1997 C ALA A 260 56.135 69.680 161.231 1.00 0.00 xxxx 1997 ATOM 1998 O ALA A 260 56.814 70.704 161.175 1.00 0.00 xxxx 1998 ATOM 1999 N LYS A 261 56.045 68.940 162.330 1.00 0.00 xxxx 1999 ATOM 2000 CA LYS A 261 56.710 69.369 163.549 1.00 0.00 xxxx 2000 ATOM 2001 CB LYS A 261 56.311 68.484 164.731 1.00 0.00 xxxx 2001 ATOM 2002 CG LYS A 261 54.865 68.702 165.160 1.00 0.00 xxxx 2002 ATOM 2003 CD LYS A 261 54.537 68.016 166.478 1.00 0.00 xxxx 2003 ATOM 2004 CE LYS A 261 53.071 68.221 166.846 1.00 0.00 xxxx 2004 ATOM 2005 NZ LYS A 261 52.725 67.634 168.170 1.00 0.00 xxxx 2005 ATOM 2006 C LYS A 261 58.224 69.387 163.372 1.00 0.00 xxxx 2006 ATOM 2007 O LYS A 261 58.870 70.364 163.743 1.00 0.00 xxxx 2007 ATOM 2008 N ASN A 262 58.800 68.333 162.797 1.00 0.00 xxxx 2008 ATOM 2009 CA ASN A 262 60.248 68.328 162.610 1.00 0.00 xxxx 2009 ATOM 2010 CB ASN A 262 60.767 66.905 162.398 1.00 0.00 xxxx 2010 ATOM 2011 CG ASN A 262 60.950 66.161 163.715 1.00 0.00 xxxx 2011 ATOM 2012 OD1 ASN A 262 61.734 66.572 164.571 1.00 0.00 xxxx 2012 ATOM 2013 ND2 ASN A 262 60.231 65.060 163.878 1.00 0.00 xxxx 2013 ATOM 2014 C ASN A 262 60.688 69.230 161.460 1.00 0.00 xxxx 2014 ATOM 2015 O ASN A 262 61.773 69.810 161.513 1.00 0.00 xxxx 2015 ATOM 2016 N GLN A 263 59.846 69.388 160.444 1.00 0.00 xxxx 2016 ATOM 2017 CA GLN A 263 60.182 70.338 159.392 1.00 0.00 xxxx 2017 ATOM 2018 CB GLN A 263 59.218 70.222 158.212 1.00 0.00 xxxx 2018 ATOM 2019 CG GLN A 263 59.489 68.968 157.391 1.00 0.00 xxxx 2019 ATOM 2020 CD GLN A 263 58.548 68.809 156.221 1.00 0.00 xxxx 2020 ATOM 2021 OE1 GLN A 263 58.355 69.734 155.431 1.00 0.00 xxxx 2021 ATOM 2022 NE2 GLN A 263 57.948 67.632 156.107 1.00 0.00 xxxx 2022 ATOM 2023 C GLN A 263 60.197 71.754 159.974 1.00 0.00 xxxx 2023 ATOM 2024 O GLN A 263 61.091 72.548 159.664 1.00 0.00 xxxx 2024 ATOM 2025 N ALA A 264 59.242 72.058 160.852 1.00 0.00 xxxx 2025 ATOM 2026 CA ALA A 264 59.205 73.371 161.488 1.00 0.00 xxxx 2026 ATOM 2027 CB ALA A 264 57.929 73.540 162.298 1.00 0.00 xxxx 2027 ATOM 2028 C ALA A 264 60.423 73.593 162.385 1.00 0.00 xxxx 2028 ATOM 2029 O ALA A 264 61.001 74.682 162.396 1.00 0.00 xxxx 2029 ATOM 2030 N LYS A 265 60.797 72.576 163.158 1.00 0.00 xxxx 2030 ATOM 2031 C LYS A 265 63.235 72.909 163.247 1.00 0.00 xxxx 2031 ATOM 2032 O LYS A 265 64.056 73.762 163.597 1.00 0.00 xxxx 2032 ATOM 2033 CA LYS A 265 61.955 72.688 164.042 1.00 0.00 xxxx 2033 ATOM 2034 CB LYS A 265 62.109 71.443 164.921 1.00 0.00 xxxx 2034 ATOM 2035 CG LYS A 265 60.962 71.194 165.866 1.00 0.00 xxxx 2035 ATOM 2036 CD LYS A 265 61.328 70.146 166.902 1.00 0.00 xxxx 2036 ATOM 2037 CE LYS A 265 60.117 69.716 167.711 1.00 0.00 xxxx 2037 ATOM 2038 NZ LYS A 265 60.514 68.939 168.913 1.00 0.00 xxxx 2038 ATOM 2039 N ALA A 266 63.409 72.146 162.171 1.00 0.00 xxxx 2039 ATOM 2040 CA ALA A 266 64.607 72.292 161.350 1.00 0.00 xxxx 2040 ATOM 2041 CB ALA A 266 64.661 71.209 160.261 1.00 0.00 xxxx 2041 ATOM 2042 C ALA A 266 64.656 73.682 160.727 1.00 0.00 xxxx 2042 ATOM 2043 O ALA A 266 65.702 74.325 160.708 1.00 0.00 xxxx 2043 ATOM 2044 N THR A 267 63.519 74.139 160.214 1.00 0.00 xxxx 2044 ATOM 2045 CA THR A 267 63.451 75.457 159.590 1.00 0.00 xxxx 2045 ATOM 2046 CB THR A 267 62.071 75.717 158.972 1.00 0.00 xxxx 2046 ATOM 2047 OG1 THR A 267 61.793 74.702 158.001 1.00 0.00 xxxx 2047 ATOM 2048 CG2 THR A 267 62.050 77.087 158.298 1.00 0.00 xxxx 2048 ATOM 2049 C THR A 267 63.769 76.550 160.594 1.00 0.00 xxxx 2049 ATOM 2050 O THR A 267 64.613 77.413 160.341 1.00 0.00 xxxx 2050 ATOM 2051 N PHE A 268 63.097 76.514 161.739 1.00 0.00 xxxx 2051 ATOM 2052 CA PHE A 268 63.396 77.493 162.764 1.00 0.00 xxxx 2052 ATOM 2053 CB PHE A 268 62.517 77.332 164.001 1.00 0.00 xxxx 2053 ATOM 2054 CG PHE A 268 62.907 78.279 165.090 1.00 0.00 xxxx 2054 ATOM 2055 CD1 PHE A 268 62.579 79.619 164.989 1.00 0.00 xxxx 2055 ATOM 2056 CE1 PHE A 268 62.971 80.513 165.958 1.00 0.00 xxxx 2056 ATOM 2057 CZ PHE A 268 63.722 80.073 167.033 1.00 0.00 xxxx 2057 ATOM 2058 CE2 PHE A 268 64.076 78.746 167.131 1.00 0.00 xxxx 2058 ATOM 2059 CD2 PHE A 268 63.679 77.855 166.161 1.00 0.00 xxxx 2059 ATOM 2060 C PHE A 268 64.858 77.423 163.204 1.00 0.00 xxxx 2060 ATOM 2061 O PHE A 268 65.507 78.456 163.318 1.00 0.00 xxxx 2061 ATOM 2062 N ASN A 269 65.367 76.219 163.467 1.00 0.00 xxxx 2062 ATOM 2063 CA ASN A 269 66.732 76.097 163.977 1.00 0.00 xxxx 2063 ATOM 2064 CB ASN A 269 67.074 74.636 164.290 1.00 0.00 xxxx 2064 ATOM 2065 CG ASN A 269 66.398 74.148 165.556 1.00 0.00 xxxx 2065 ATOM 2066 OD1 ASN A 269 65.773 74.931 166.270 1.00 0.00 xxxx 2066 ATOM 2067 ND2 ASN A 269 66.531 72.858 165.852 1.00 0.00 xxxx 2067 ATOM 2068 C ASN A 269 67.744 76.682 162.996 1.00 0.00 xxxx 2068 ATOM 2069 O ASN A 269 68.693 77.350 163.408 1.00 0.00 xxxx 2069 ATOM 2070 N ILE A 270 67.527 76.457 161.705 1.00 0.00 xxxx 2070 ATOM 2071 CA ILE A 270 68.428 77.004 160.704 1.00 0.00 xxxx 2071 ATOM 2072 CB ILE A 270 68.120 76.434 159.308 1.00 0.00 xxxx 2072 ATOM 2073 CG1 ILE A 270 68.529 74.959 159.220 1.00 0.00 xxxx 2073 ATOM 2074 CD1 ILE A 270 68.081 74.296 157.903 1.00 0.00 xxxx 2074 ATOM 2075 CG2 ILE A 270 68.811 77.279 158.217 1.00 0.00 xxxx 2075 ATOM 2076 C ILE A 270 68.360 78.532 160.701 1.00 0.00 xxxx 2076 ATOM 2077 O ILE A 270 69.394 79.200 160.723 1.00 0.00 xxxx 2077 ATOM 2078 N ALA A 271 67.148 79.083 160.699 1.00 0.00 xxxx 2078 ATOM 2079 CA ALA A 271 66.969 80.538 160.675 1.00 0.00 xxxx 2079 ATOM 2080 CB ALA A 271 65.482 80.900 160.547 1.00 0.00 xxxx 2080 ATOM 2081 C ALA A 271 67.569 81.163 161.928 1.00 0.00 xxxx 2081 ATOM 2082 O ALA A 271 68.144 82.248 161.877 1.00 0.00 xxxx 2082 ATOM 2083 N TYR A 272 67.439 80.457 163.047 1.00 0.00 xxxx 2083 ATOM 2084 CA TYR A 272 67.902 80.941 164.340 1.00 0.00 xxxx 2084 ATOM 2085 CB TYR A 272 67.345 80.034 165.445 1.00 0.00 xxxx 2085 ATOM 2086 CG TYR A 272 67.624 80.441 166.876 1.00 0.00 xxxx 2086 ATOM 2087 CD1 TYR A 272 67.292 81.704 167.345 1.00 0.00 xxxx 2087 ATOM 2088 CE1 TYR A 272 67.527 82.060 168.663 1.00 0.00 xxxx 2088 ATOM 2089 CZ TYR A 272 68.082 81.142 169.528 1.00 0.00 xxxx 2089 ATOM 2090 OH TYR A 272 68.318 81.500 170.838 1.00 0.00 xxxx 2090 ATOM 2091 CE2 TYR A 272 68.407 79.877 169.092 1.00 0.00 xxxx 2091 ATOM 2092 CD2 TYR A 272 68.165 79.529 167.773 1.00 0.00 xxxx 2092 ATOM 2093 C TYR A 272 69.426 80.990 164.382 1.00 0.00 xxxx 2093 ATOM 2094 O TYR A 272 70.008 81.970 164.852 1.00 0.00 xxxx 2094 ATOM 2095 N GLU A 273 70.076 79.939 163.879 1.00 0.00 xxxx 2095 ATOM 2096 CA GLU A 273 71.533 79.939 163.820 1.00 0.00 xxxx 2096 ATOM 2097 CB GLU A 273 72.076 78.576 163.385 1.00 0.00 xxxx 2097 ATOM 2098 CG GLU A 273 71.808 77.455 164.387 1.00 0.00 xxxx 2098 ATOM 2099 CD GLU A 273 72.396 77.727 165.771 1.00 0.00 xxxx 2099 ATOM 2100 OE1 GLU A 273 73.574 78.132 165.864 1.00 0.00 xxxx 2100 ATOM 2101 OE2 GLU A 273 71.674 77.533 166.771 1.00 0.00 xxxx 2101 ATOM 2102 C GLU A 273 72.017 81.037 162.873 1.00 0.00 xxxx 2102 ATOM 2103 O GLU A 273 72.927 81.795 163.210 1.00 0.00 xxxx 2103 ATOM 2104 N LEU A 274 71.394 81.136 161.701 1.00 0.00 xxxx 2104 ATOM 2105 CA LEU A 274 71.817 82.128 160.715 1.00 0.00 xxxx 2105 ATOM 2106 CB LEU A 274 71.085 81.928 159.385 1.00 0.00 xxxx 2106 ATOM 2107 CG LEU A 274 71.476 80.692 158.562 1.00 0.00 xxxx 2107 ATOM 2108 CD1 LEU A 274 70.465 80.446 157.451 1.00 0.00 xxxx 2108 ATOM 2109 CD2 LEU A 274 72.894 80.826 158.000 1.00 0.00 xxxx 2109 ATOM 2110 C LEU A 274 71.592 83.545 161.240 1.00 0.00 xxxx 2110 ATOM 2111 O LEU A 274 72.384 84.450 160.968 1.00 0.00 xxxx 2111 ATOM 2112 N ALA A 275 70.533 83.727 162.023 1.00 0.00 xxxx 2112 ATOM 2113 CA ALA A 275 70.234 85.034 162.599 1.00 0.00 xxxx 2113 ATOM 2114 CB ALA A 275 68.877 85.021 163.283 1.00 0.00 xxxx 2114 ATOM 2115 C ALA A 275 71.323 85.449 163.585 1.00 0.00 xxxx 2115 ATOM 2116 O ALA A 275 71.541 86.641 163.813 1.00 0.00 xxxx 2116 ATOM 2117 N GLN A 276 71.997 84.458 164.165 1.00 0.00 xxxx 2117 ATOM 2118 CA GLN A 276 73.079 84.706 165.120 1.00 0.00 xxxx 2118 ATOM 2119 CB GLN A 276 73.124 83.613 166.189 1.00 0.00 xxxx 2119 ATOM 2120 CG GLN A 276 71.901 83.542 167.092 1.00 0.00 xxxx 2120 ATOM 2121 CD GLN A 276 71.914 82.318 167.986 1.00 0.00 xxxx 2121 ATOM 2122 OE1 GLN A 276 71.240 81.323 167.708 1.00 0.00 xxxx 2122 ATOM 2123 NE2 GLN A 276 72.690 82.381 169.066 1.00 0.00 xxxx 2123 ATOM 2124 C GLN A 276 74.442 84.790 164.440 1.00 0.00 xxxx 2124 ATOM 2125 O GLN A 276 75.461 84.971 165.110 1.00 0.00 xxxx 2125 ATOM 2126 N GLY A 277 74.461 84.662 163.119 1.00 0.00 xxxx 2126 ATOM 2127 CA GLY A 277 75.708 84.670 162.372 1.00 0.00 xxxx 2127 ATOM 2128 C GLY A 277 76.469 83.358 162.461 1.00 0.00 xxxx 2128 ATOM 2129 O GLY A 277 77.673 83.303 162.200 1.00 0.00 xxxx 2129 ATOM 2130 N ILE A 278 75.762 82.293 162.823 1.00 0.00 xxxx 2130 ATOM 2131 CA ILE A 278 76.368 80.971 162.968 1.00 0.00 xxxx 2131 ATOM 2132 CB ILE A 278 75.943 80.326 164.299 1.00 0.00 xxxx 2132 ATOM 2133 CG1 ILE A 278 76.389 81.209 165.470 1.00 0.00 xxxx 2133 ATOM 2134 CD1 ILE A 278 75.767 80.832 166.795 1.00 0.00 xxxx 2134 ATOM 2135 CG2 ILE A 278 76.495 78.904 164.424 1.00 0.00 xxxx 2135 ATOM 2136 C ILE A 278 75.998 80.078 161.782 1.00 0.00 xxxx 2136 ATOM 2137 O ILE A 278 74.836 80.015 161.380 1.00 0.00 xxxx 2137 ATOM 2138 N THR A 279 76.988 79.390 161.221 1.00 0.00 xxxx 2138 ATOM 2139 CA THR A 279 76.737 78.469 160.112 1.00 0.00 xxxx 2139 ATOM 2140 CB THR A 279 78.040 78.105 159.374 1.00 0.00 xxxx 2140 ATOM 2141 OG1 THR A 279 78.635 79.296 158.841 1.00 0.00 xxxx 2141 ATOM 2142 CG2 THR A 279 77.760 77.132 158.245 1.00 0.00 xxxx 2142 ATOM 2143 C THR A 279 76.078 77.186 160.609 1.00 0.00 xxxx 2143 ATOM 2144 O THR A 279 76.610 76.533 161.506 1.00 0.00 xxxx 2144 ATOM 2145 N PRO A 280 74.920 76.819 160.027 1.00 0.00 xxxx 2145 ATOM 2146 CA PRO A 280 74.256 75.568 160.417 1.00 0.00 xxxx 2146 ATOM 2147 CB PRO A 280 73.070 75.489 159.450 1.00 0.00 xxxx 2147 ATOM 2148 CG PRO A 280 72.751 76.924 159.144 1.00 0.00 xxxx 2148 ATOM 2149 CD PRO A 280 74.092 77.612 159.097 1.00 0.00 xxxx 2149 ATOM 2150 C PRO A 280 75.140 74.329 160.279 1.00 0.00 xxxx 2150 ATOM 2151 O PRO A 280 75.859 74.177 159.290 1.00 0.00 xxxx 2151 ATOM 2152 N THR A 281 75.102 73.472 161.295 1.00 0.00 xxxx 2152 ATOM 2153 CA THR A 281 75.739 72.155 161.265 1.00 0.00 xxxx 2153 ATOM 2154 CB THR A 281 77.009 72.086 162.122 1.00 0.00 xxxx 2154 ATOM 2155 OG1 THR A 281 76.650 72.211 163.503 1.00 0.00 xxxx 2155 ATOM 2156 CG2 THR A 281 77.978 73.199 161.759 1.00 0.00 xxxx 2156 ATOM 2157 C THR A 281 74.728 71.158 161.808 1.00 0.00 xxxx 2157 ATOM 2158 O THR A 281 73.770 71.560 162.466 1.00 0.00 xxxx 2158 ATOM 2159 N LYS A 282 74.939 69.868 161.558 1.00 0.00 xxxx 2159 ATOM 2160 CA LYS A 282 74.074 68.851 162.146 1.00 0.00 xxxx 2160 ATOM 2161 CB LYS A 282 74.540 67.441 161.777 1.00 0.00 xxxx 2161 ATOM 2162 CG LYS A 282 73.709 66.356 162.445 1.00 0.00 xxxx 2162 ATOM 2163 CD LYS A 282 74.069 64.971 161.951 1.00 0.00 xxxx 2163 ATOM 2164 CE LYS A 282 73.131 63.935 162.548 1.00 0.00 xxxx 2164 ATOM 2165 NZ LYS A 282 73.423 62.568 162.033 1.00 0.00 xxxx 2165 ATOM 2166 C LYS A 282 74.026 68.995 163.667 1.00 0.00 xxxx 2166 ATOM 2167 O LYS A 282 72.974 68.811 164.278 1.00 0.00 xxxx 2167 ATOM 2168 N ASP A 283 75.156 69.342 164.274 1.00 0.00 xxxx 2168 ATOM 2169 CA ASP A 283 75.208 69.504 165.719 1.00 0.00 xxxx 2169 ATOM 2170 CB ASP A 283 76.646 69.739 166.193 1.00 0.00 xxxx 2170 ATOM 2171 CG ASP A 283 77.478 68.474 166.201 1.00 0.00 xxxx 2171 ATOM 2172 OD1 ASP A 283 76.920 67.381 165.965 1.00 0.00 xxxx 2172 ATOM 2173 OD2 ASP A 283 78.698 68.576 166.461 1.00 0.00 xxxx 2173 ATOM 2174 C ASP A 283 74.329 70.651 166.217 1.00 0.00 xxxx 2174 ATOM 2175 O ASP A 283 73.639 70.501 167.228 1.00 0.00 xxxx 2175 ATOM 2176 N ASN A 284 74.353 71.799 165.539 1.00 0.00 xxxx 2176 ATOM 2177 CA ASN A 284 73.670 72.962 166.110 1.00 0.00 xxxx 2177 ATOM 2178 CB ASN A 284 74.506 74.254 165.920 1.00 0.00 xxxx 2178 ATOM 2179 CG ASN A 284 74.696 74.658 164.461 1.00 0.00 xxxx 2179 ATOM 2180 OD1 ASN A 284 73.869 74.373 163.603 1.00 0.00 xxxx 2180 ATOM 2181 ND2 ASN A 284 75.793 75.361 164.188 1.00 0.00 xxxx 2181 ATOM 2182 C ASN A 284 72.237 73.163 165.593 1.00 0.00 xxxx 2182 ATOM 2183 O ASN A 284 71.515 73.997 166.135 1.00 0.00 xxxx 2183 ATOM 2184 N ILE A 285 71.805 72.403 164.581 1.00 0.00 xxxx 2184 ATOM 2185 CA ILE A 285 70.383 72.428 164.228 1.00 0.00 xxxx 2185 ATOM 2186 CB ILE A 285 70.154 72.786 162.739 1.00 0.00 xxxx 2186 ATOM 2187 CG1 ILE A 285 70.630 71.667 161.808 1.00 0.00 xxxx 2187 ATOM 2188 CD1 ILE A 285 70.062 71.779 160.390 1.00 0.00 xxxx 2188 ATOM 2189 CG2 ILE A 285 70.809 74.122 162.399 1.00 0.00 xxxx 2189 ATOM 2190 C ILE A 285 69.662 71.116 164.557 1.00 0.00 xxxx 2190 ATOM 2191 O ILE A 285 68.431 71.087 164.592 1.00 0.00 xxxx 2191 ATOM 2192 N GLY A 286 70.414 70.040 164.782 1.00 0.00 xxxx 2192 ATOM 2193 CA GLY A 286 69.830 68.779 165.210 1.00 0.00 xxxx 2193 ATOM 2194 C GLY A 286 69.321 67.841 164.134 1.00 0.00 xxxx 2194 ATOM 2195 O GLY A 286 68.576 66.908 164.437 1.00 0.00 xxxx 2195 ATOM 2196 N TYR A 287 69.718 68.088 162.883 1.00 0.00 xxxx 2196 ATOM 2197 CA TYR A 287 69.293 67.281 161.736 1.00 0.00 xxxx 2197 ATOM 2198 CB TYR A 287 68.093 67.922 161.026 1.00 0.00 xxxx 2198 ATOM 2199 CG TYR A 287 66.884 68.058 161.911 1.00 0.00 xxxx 2199 ATOM 2200 CD1 TYR A 287 66.708 69.188 162.701 1.00 0.00 xxxx 2200 ATOM 2201 CE1 TYR A 287 65.613 69.318 163.527 1.00 0.00 xxxx 2201 ATOM 2202 CZ TYR A 287 64.674 68.312 163.570 1.00 0.00 xxxx 2202 ATOM 2203 OH TYR A 287 63.586 68.449 164.405 1.00 0.00 xxxx 2203 ATOM 2204 CE2 TYR A 287 64.823 67.171 162.795 1.00 0.00 xxxx 2204 ATOM 2205 CD2 TYR A 287 65.923 67.052 161.965 1.00 0.00 xxxx 2205 ATOM 2206 C TYR A 287 70.428 67.138 160.738 1.00 0.00 xxxx 2206 ATOM 2207 O TYR A 287 71.245 68.048 160.609 1.00 0.00 xxxx 2207 ATOM 2208 N ASP A 288 70.469 66.004 160.034 1.00 0.00 xxxx 2208 ATOM 2209 CA ASP A 288 71.399 65.819 158.918 1.00 0.00 xxxx 2209 ATOM 2210 CB ASP A 288 71.210 64.445 158.269 1.00 0.00 xxxx 2210 ATOM 2211 CG ASP A 288 71.732 63.318 159.118 1.00 0.00 xxxx 2211 ATOM 2212 OD1 ASP A 288 72.927 63.343 159.473 1.00 0.00 xxxx 2212 ATOM 2213 OD2 ASP A 288 70.942 62.397 159.416 1.00 0.00 xxxx 2213 ATOM 2214 C ASP A 288 71.203 66.877 157.843 1.00 0.00 xxxx 2214 ATOM 2215 O ASP A 288 70.071 67.186 157.466 1.00 0.00 xxxx 2215 ATOM 2216 N ILE A 289 72.311 67.412 157.340 1.00 0.00 xxxx 2216 ATOM 2217 CA ILE A 289 72.280 68.351 156.219 1.00 0.00 xxxx 2217 ATOM 2218 CB ILE A 289 73.095 69.615 156.517 1.00 0.00 xxxx 2218 ATOM 2219 CG1 ILE A 289 72.558 70.310 157.769 1.00 0.00 xxxx 2219 ATOM 2220 CD1 ILE A 289 73.458 71.434 158.271 1.00 0.00 xxxx 2220 ATOM 2221 CG2 ILE A 289 73.059 70.575 155.321 1.00 0.00 xxxx 2221 ATOM 2222 C ILE A 289 72.810 67.618 154.995 1.00 0.00 xxxx 2222 ATOM 2223 O ILE A 289 73.862 66.978 155.052 1.00 0.00 xxxx 2223 ATOM 2224 N THR A 290 72.066 67.701 153.898 1.00 0.00 xxxx 2224 ATOM 2225 CA THR A 290 72.393 66.983 152.668 1.00 0.00 xxxx 2225 ATOM 2226 CB THR A 290 71.173 66.165 152.178 1.00 0.00 xxxx 2226 ATOM 2227 OG1 THR A 290 70.769 65.253 153.204 1.00 0.00 xxxx 2227 ATOM 2228 CG2 THR A 290 71.496 65.377 150.909 1.00 0.00 xxxx 2228 ATOM 2229 C THR A 290 72.829 67.970 151.588 1.00 0.00 xxxx 2229 ATOM 2230 O THR A 290 72.252 69.046 151.462 1.00 0.00 xxxx 2230 ATOM 2231 N ASP A 291 73.872 67.620 150.841 1.00 0.00 xxxx 2231 ATOM 2232 CA ASP A 291 74.367 68.479 149.764 1.00 0.00 xxxx 2232 ATOM 2233 CB ASP A 291 73.338 68.541 148.614 1.00 0.00 xxxx 2233 ATOM 2234 CG ASP A 291 73.206 67.219 147.865 1.00 0.00 xxxx 2234 ATOM 2235 OD1 ASP A 291 74.245 66.647 147.474 1.00 0.00 xxxx 2235 ATOM 2236 OD2 ASP A 291 72.065 66.754 147.659 1.00 0.00 xxxx 2236 ATOM 2237 C ASP A 291 74.696 69.891 150.274 1.00 0.00 xxxx 2237 ATOM 2238 O ASP A 291 74.624 70.873 149.532 1.00 0.00 xxxx 2238 ATOM 2239 N GLY A 292 75.068 69.984 151.546 1.00 0.00 xxxx 2239 ATOM 2240 CA GLY A 292 75.441 71.251 152.152 1.00 0.00 xxxx 2240 ATOM 2241 C GLY A 292 74.328 72.257 152.390 1.00 0.00 xxxx 2241 ATOM 2242 O GLY A 292 74.558 73.299 153.006 1.00 0.00 xxxx 2242 ATOM 2243 N LYS A 293 73.118 71.958 151.920 1.00 0.00 xxxx 2243 ATOM 2244 CA LYS A 293 72.054 72.963 151.908 1.00 0.00 xxxx 2244 ATOM 2245 CB LYS A 293 71.920 73.565 150.505 1.00 0.00 xxxx 2245 ATOM 2246 CG LYS A 293 73.118 74.371 150.044 1.00 0.00 xxxx 2246 ATOM 2247 CD LYS A 293 72.954 74.836 148.612 1.00 0.00 xxxx 2247 ATOM 2248 CE LYS A 293 74.246 75.471 148.090 1.00 0.00 xxxx 2248 ATOM 2249 NZ LYS A 293 74.399 76.899 148.510 1.00 0.00 xxxx 2249 ATOM 2250 C LYS A 293 70.676 72.474 152.330 1.00 0.00 xxxx 2250 ATOM 2251 O LYS A 293 69.810 73.296 152.635 1.00 0.00 xxxx 2251 ATOM 2252 N TYR A 294 70.456 71.161 152.316 1.00 0.00 xxxx 2252 ATOM 2253 CA TYR A 294 69.104 70.620 152.456 1.00 0.00 xxxx 2253 ATOM 2254 CB TYR A 294 68.762 69.680 151.294 1.00 0.00 xxxx 2254 ATOM 2255 CG TYR A 294 68.805 70.293 149.917 1.00 0.00 xxxx 2255 ATOM 2256 CD1 TYR A 294 69.996 70.361 149.205 1.00 0.00 xxxx 2256 ATOM 2257 CE1 TYR A 294 70.032 70.915 147.941 1.00 0.00 xxxx 2257 ATOM 2258 CZ TYR A 294 68.863 71.389 147.366 1.00 0.00 xxxx 2258 ATOM 2259 OH TYR A 294 68.908 71.929 146.098 1.00 0.00 xxxx 2259 ATOM 2260 CE2 TYR A 294 67.672 71.319 148.046 1.00 0.00 xxxx 2260 ATOM 2261 CD2 TYR A 294 67.651 70.777 149.318 1.00 0.00 xxxx 2261 ATOM 2262 C TYR A 294 68.910 69.839 153.739 1.00 0.00 xxxx 2262 ATOM 2263 O TYR A 294 69.782 69.065 154.135 1.00 0.00 xxxx 2263 ATOM 2264 N VAL A 295 67.751 70.013 154.365 1.00 0.00 xxxx 2264 ATOM 2265 CA VAL A 295 67.357 69.122 155.445 1.00 0.00 xxxx 2265 ATOM 2266 CB VAL A 295 67.101 69.874 156.749 1.00 0.00 xxxx 2266 ATOM 2267 CG1 VAL A 295 66.510 68.914 157.789 1.00 0.00 xxxx 2267 ATOM 2268 CG2 VAL A 295 68.402 70.504 157.263 1.00 0.00 xxxx 2268 ATOM 2269 C VAL A 295 66.116 68.350 155.008 1.00 0.00 xxxx 2269 ATOM 2270 O VAL A 295 65.059 68.939 154.769 1.00 0.00 xxxx 2270 ATOM 2271 N TRP A 296 66.274 67.037 154.876 1.00 0.00 xxxx 2271 ATOM 2272 CA TRP A 296 65.187 66.147 154.483 1.00 0.00 xxxx 2272 ATOM 2273 CB TRP A 296 65.668 65.135 153.441 1.00 0.00 xxxx 2273 ATOM 2274 CG TRP A 296 66.233 65.760 152.203 1.00 0.00 xxxx 2274 ATOM 2275 CD1 TRP A 296 67.529 65.712 151.778 1.00 0.00 xxxx 2275 ATOM 2276 NE1 TRP A 296 67.665 66.395 150.595 1.00 0.00 xxxx 2276 ATOM 2277 CE2 TRP A 296 66.449 66.922 150.244 1.00 0.00 xxxx 2277 ATOM 2278 CD2 TRP A 296 65.522 66.542 151.235 1.00 0.00 xxxx 2278 ATOM 2279 CE3 TRP A 296 64.192 66.955 151.110 1.00 0.00 xxxx 2279 ATOM 2280 CZ3 TRP A 296 63.831 67.718 150.011 1.00 0.00 xxxx 2280 ATOM 2281 CH2 TRP A 296 64.776 68.082 149.041 1.00 0.00 xxxx 2281 ATOM 2282 CZ2 TRP A 296 66.091 67.694 149.141 1.00 0.00 xxxx 2282 ATOM 2283 C TRP A 296 64.626 65.422 155.691 1.00 0.00 xxxx 2283 ATOM 2284 O TRP A 296 65.356 64.767 156.437 1.00 0.00 xxxx 2284 ATOM 2285 N ILE A 297 63.319 65.556 155.886 1.00 0.00 xxxx 2285 ATOM 2286 CA ILE A 297 62.625 64.918 156.991 1.00 0.00 xxxx 2286 ATOM 2287 CB ILE A 297 61.670 65.912 157.681 1.00 0.00 xxxx 2287 ATOM 2288 CG1 ILE A 297 62.442 67.139 158.205 1.00 0.00 xxxx 2288 ATOM 2289 CD1 ILE A 297 63.572 66.805 159.187 1.00 0.00 xxxx 2289 ATOM 2290 CG2 ILE A 297 60.875 65.225 158.779 1.00 0.00 xxxx 2290 ATOM 2291 C ILE A 297 61.860 63.716 156.435 1.00 0.00 xxxx 2291 ATOM 2292 O ILE A 297 61.168 63.845 155.428 1.00 0.00 xxxx 2292 ATOM 2293 N PRO A 298 61.994 62.544 157.072 1.00 0.00 xxxx 2293 ATOM 2294 CA PRO A 298 61.335 61.350 156.526 1.00 0.00 xxxx 2294 ATOM 2295 CB PRO A 298 61.776 60.232 157.476 1.00 0.00 xxxx 2295 ATOM 2296 CG PRO A 298 63.030 60.727 158.091 1.00 0.00 xxxx 2296 ATOM 2297 CD PRO A 298 62.879 62.218 158.201 1.00 0.00 xxxx 2297 ATOM 2298 C PRO A 298 59.814 61.425 156.506 1.00 0.00 xxxx 2298 ATOM 2299 O PRO A 298 59.187 62.048 157.366 1.00 0.00 xxxx 2299 ATOM 2300 N TYR A 299 59.248 60.763 155.507 1.00 0.00 xxxx 2300 ATOM 2301 CA TYR A 299 57.828 60.450 155.457 1.00 0.00 xxxx 2301 ATOM 2302 CB TYR A 299 57.354 60.373 154.019 1.00 0.00 xxxx 2302 ATOM 2303 CG TYR A 299 57.128 61.683 153.320 1.00 0.00 xxxx 2303 ATOM 2304 CD1 TYR A 299 56.016 62.464 153.623 1.00 0.00 xxxx 2304 ATOM 2305 CE1 TYR A 299 55.781 63.651 152.964 1.00 0.00 xxxx 2305 ATOM 2306 CZ TYR A 299 56.642 64.066 151.973 1.00 0.00 xxxx 2306 ATOM 2307 OH TYR A 299 56.379 65.254 151.326 1.00 0.00 xxxx 2307 ATOM 2308 CE2 TYR A 299 57.753 63.298 151.630 1.00 0.00 xxxx 2308 ATOM 2309 CD2 TYR A 299 57.987 62.117 152.310 1.00 0.00 xxxx 2309 ATOM 2310 C TYR A 299 57.579 59.107 156.120 1.00 0.00 xxxx 2310 ATOM 2311 O TYR A 299 58.478 58.275 156.169 1.00 0.00 xxxx 2311 ATOM 2312 N LYS A 300 56.348 58.873 156.572 1.00 0.00 xxxx 2312 ATOM 2313 CA LYS A 300 55.993 57.607 157.212 1.00 0.00 xxxx 2313 ATOM 2314 CB LYS A 300 56.044 57.758 158.737 1.00 0.00 xxxx 2314 ATOM 2315 CG LYS A 300 55.632 56.512 159.500 1.00 0.00 xxxx 2315 ATOM 2316 CD LYS A 300 55.948 56.652 160.981 1.00 0.00 xxxx 2316 ATOM 2317 CE LYS A 300 55.732 55.342 161.715 1.00 0.00 xxxx 2317 ATOM 2318 NZ LYS A 300 56.541 54.228 161.143 1.00 0.00 xxxx 2318 ATOM 2319 C LYS A 300 54.601 57.129 156.772 1.00 0.00 xxxx 2319 ATOM 2320 O LYS A 300 53.637 57.899 156.808 1.00 0.00 xxxx 2320 ATOM 2321 N LYS A 301 54.493 55.862 156.376 1.00 0.00 xxxx 2321 ATOM 2322 CA LYS A 301 53.200 55.299 155.946 1.00 0.00 xxxx 2322 ATOM 2323 CB LYS A 301 53.409 53.910 155.323 1.00 0.00 xxxx 2323 ATOM 2324 CG LYS A 301 52.154 53.289 154.718 1.00 0.00 xxxx 2324 ATOM 2325 CD LYS A 301 52.372 51.812 154.360 1.00 0.00 xxxx 2325 ATOM 2326 CE LYS A 301 53.431 51.658 153.267 1.00 0.00 xxxx 2326 ATOM 2327 NZ LYS A 301 53.686 50.216 152.948 1.00 0.00 xxxx 2327 ATOM 2328 C LYS A 301 52.212 55.213 157.116 1.00 0.00 xxxx 2328 ATOM 2329 O LYS A 301 52.585 54.798 158.215 1.00 0.00 xxxx 2329 ATOM 2330 N ILE A 302 50.959 55.605 156.873 1.00 0.00 xxxx 2330 ATOM 2331 CA ILE A 302 49.900 55.566 157.892 1.00 0.00 xxxx 2331 ATOM 2332 CB ILE A 302 49.534 56.984 158.400 1.00 0.00 xxxx 2332 ATOM 2333 CG1 ILE A 302 50.755 57.717 158.975 1.00 0.00 xxxx 2333 ATOM 2334 CD1 ILE A 302 51.290 57.107 160.271 1.00 0.00 xxxx 2334 ATOM 2335 CG2 ILE A 302 48.379 56.906 159.406 1.00 0.00 xxxx 2335 ATOM 2336 C ILE A 302 48.642 54.893 157.348 1.00 0.00 xxxx 2336 ATOM 2337 O ILE A 302 48.058 55.349 156.350 1.00 0.00 xxxx 2337 ATOM 2338 N THR A 303 48.217 53.815 158.003 1.00 0.00 xxxx 2338 ATOM 2339 CA THR A 303 46.919 53.208 157.730 1.00 0.00 xxxx 2339 ATOM 2340 CB THR A 303 47.028 51.873 156.955 1.00 0.00 xxxx 2340 ATOM 2341 OG1 THR A 303 47.652 50.881 157.783 1.00 0.00 xxxx 2341 ATOM 2342 CG2 THR A 303 47.839 52.044 155.668 1.00 0.00 xxxx 2342 ATOM 2343 C THR A 303 46.224 52.959 159.061 1.00 0.00 xxxx 2343 ATOM 2344 O THR A 303 46.742 53.339 160.115 1.00 0.00 xxxx 2344 ATOM 2345 N LYS A 304 45.062 52.310 159.031 1.00 0.00 xxxx 2345 ATOM 2346 CA LYS A 304 44.365 52.034 160.284 1.00 0.00 xxxx 2346 ATOM 2347 CB LYS A 304 43.014 51.356 160.027 1.00 0.00 xxxx 2347 ATOM 2348 CG LYS A 304 43.113 49.981 159.388 1.00 0.00 xxxx 2348 ATOM 2349 CD LYS A 304 41.728 49.408 159.091 1.00 0.00 xxxx 2349 ATOM 2350 CE LYS A 304 41.817 48.045 158.422 1.00 0.00 xxxx 2350 ATOM 2351 NZ LYS A 304 40.513 47.632 157.829 1.00 0.00 xxxx 2351 ATOM 2352 C LYS A 304 45.224 51.168 161.207 1.00 0.00 xxxx 2352 ATOM 2353 O LYS A 304 45.055 51.198 162.423 1.00 0.00 xxxx 2353 ATOM 2354 N ASP A 305 46.162 50.421 160.626 1.00 0.00 xxxx 2354 ATOM 2355 CA ASP A 305 47.010 49.503 161.393 1.00 0.00 xxxx 2355 ATOM 2356 CB ASP A 305 47.778 48.575 160.446 1.00 0.00 xxxx 2356 ATOM 2357 CG ASP A 305 46.869 47.611 159.704 1.00 0.00 xxxx 2357 ATOM 2358 OD1 ASP A 305 45.789 47.276 160.236 1.00 0.00 xxxx 2358 ATOM 2359 OD2 ASP A 305 47.240 47.187 158.588 1.00 0.00 xxxx 2359 ATOM 2360 C ASP A 305 48.002 50.209 162.316 1.00 0.00 xxxx 2360 ATOM 2361 O ASP A 305 48.483 49.618 163.280 1.00 0.00 xxxx 2361 ATOM 2362 N ASN A 306 48.314 51.466 162.026 1.00 0.00 xxxx 2362 ATOM 2363 CA ASN A 306 49.287 52.189 162.835 1.00 0.00 xxxx 2363 ATOM 2364 CB ASN A 306 50.698 52.038 162.248 1.00 0.00 xxxx 2364 ATOM 2365 CG ASN A 306 50.854 52.713 160.891 1.00 0.00 xxxx 2365 ATOM 2366 OD1 ASN A 306 49.928 52.732 160.082 1.00 0.00 xxxx 2366 ATOM 2367 ND2 ASN A 306 52.037 53.261 160.637 1.00 0.00 xxxx 2367 ATOM 2368 C ASN A 306 48.918 53.660 162.969 1.00 0.00 xxxx 2368 ATOM 2369 O ASN A 306 49.786 54.536 162.985 1.00 0.00 xxxx 2369 ATOM 2370 N ILE A 307 47.618 53.920 163.088 1.00 0.00 xxxx 2370 ATOM 2371 CA ILE A 307 47.113 55.284 163.115 1.00 0.00 xxxx 2371 ATOM 2372 CB ILE A 307 45.566 55.285 163.204 1.00 0.00 xxxx 2372 ATOM 2373 CG1 ILE A 307 45.008 56.676 162.905 1.00 0.00 xxxx 2373 ATOM 2374 CD1 ILE A 307 45.401 57.215 161.543 1.00 0.00 xxxx 2374 ATOM 2375 CG2 ILE A 307 45.101 54.783 164.565 1.00 0.00 xxxx 2375 ATOM 2376 C ILE A 307 47.740 56.099 164.252 1.00 0.00 xxxx 2376 ATOM 2377 O ILE A 307 47.861 57.320 164.148 1.00 0.00 xxxx 2377 ATOM 2378 N SER A 308 48.172 55.431 165.320 1.00 0.00 xxxx 2378 ATOM 2379 CA SER A 308 48.767 56.141 166.452 1.00 0.00 xxxx 2379 ATOM 2380 CB SER A 308 48.875 55.219 167.673 1.00 0.00 xxxx 2380 ATOM 2381 OG SER A 308 49.886 54.245 167.496 1.00 0.00 xxxx 2381 ATOM 2382 C SER A 308 50.141 56.731 166.124 1.00 0.00 xxxx 2382 ATOM 2383 O SER A 308 50.586 57.664 166.790 1.00 0.00 xxxx 2383 ATOM 2384 N ASP A 309 50.805 56.205 165.095 1.00 0.00 xxxx 2384 ATOM 2385 CA ASP A 309 52.090 56.752 164.660 1.00 0.00 xxxx 2385 ATOM 2386 CB ASP A 309 52.726 55.882 163.569 1.00 0.00 xxxx 2386 ATOM 2387 CG ASP A 309 53.171 54.518 164.078 1.00 0.00 xxxx 2387 ATOM 2388 OD1 ASP A 309 53.127 54.286 165.307 1.00 0.00 xxxx 2388 ATOM 2389 OD2 ASP A 309 53.576 53.678 163.241 1.00 0.00 xxxx 2389 ATOM 2390 C ASP A 309 51.934 58.179 164.141 1.00 0.00 xxxx 2390 ATOM 2391 O ASP A 309 52.904 58.931 164.058 1.00 0.00 xxxx 2391 ATOM 2392 N ALA A 310 50.708 58.547 163.779 1.00 0.00 xxxx 2392 ATOM 2393 CA ALA A 310 50.434 59.898 163.299 1.00 0.00 xxxx 2393 ATOM 2394 CB ALA A 310 49.382 59.865 162.204 1.00 0.00 xxxx 2394 ATOM 2395 C ALA A 310 49.984 60.816 164.433 1.00 0.00 xxxx 2395 ATOM 2396 O ALA A 310 49.930 62.035 164.267 1.00 0.00 xxxx 2396 ATOM 2397 N GLU A 311 49.659 60.222 165.578 1.00 0.00 xxxx 2397 ATOM 2398 CA GLU A 311 49.189 60.972 166.740 1.00 0.00 xxxx 2398 ATOM 2399 CB GLU A 311 47.813 60.467 167.181 1.00 0.00 xxxx 2399 ATOM 2400 CG GLU A 311 46.695 60.765 166.192 1.00 0.00 xxxx 2400 ATOM 2401 CD GLU A 311 45.341 60.264 166.667 1.00 0.00 xxxx 2401 ATOM 2402 OE1 GLU A 311 45.230 59.066 167.007 1.00 0.00 xxxx 2402 ATOM 2403 OE2 GLU A 311 44.389 61.074 166.706 1.00 0.00 xxxx 2403 ATOM 2404 C GLU A 311 50.176 60.877 167.901 1.00 0.00 xxxx 2404 ATOM 2405 O GLU A 311 51.196 61.567 167.922 1.00 0.00 xxxx 2405 HETATM 2406 CA CA B 1 39.371 47.012 136.545 1.00 0.00 xxxx 2406 HETATM 2407 C1 GLC D 1 52.565 69.686 150.506 1.00 0.00 xxxx 2407 HETATM 2408 O1 GLC D 1 53.728 69.129 150.956 1.00 0.00 xxxx 2408 HETATM 2409 C2 GLC D 1 51.391 69.237 151.365 1.00 0.00 xxxx 2409 HETATM 2410 O2 GLC D 1 51.234 67.810 151.200 1.00 0.00 xxxx 2410 HETATM 2411 C3 GLC D 1 50.148 69.960 150.972 1.00 0.00 xxxx 2411 HETATM 2412 O3 GLC D 1 49.046 69.627 151.871 1.00 0.00 xxxx 2412 HETATM 2413 C4 GLC D 1 50.326 71.452 150.956 1.00 0.00 xxxx 2413 HETATM 2414 O4 GLC D 1 49.123 72.037 150.423 1.00 0.00 xxxx 2414 HETATM 2415 C5 GLC D 1 51.531 71.878 150.110 1.00 0.00 xxxx 2415 HETATM 2416 O5 GLC D 1 52.725 71.167 150.570 1.00 0.00 xxxx 2416 HETATM 2417 C6 GLC D 1 51.798 73.355 150.257 1.00 0.00 xxxx 2417 HETATM 2418 O6 GLC D 1 53.018 73.737 149.650 1.00 0.00 xxxx 2418 HETATM 2419 K K E 1 31.330 50.918 152.438 1.00 0.00 xxxx 2419 HETATM 2420 O15 BAD H 1 51.518 67.880 156.090 1.00 0.00 xxxx 2420 HETATM 2421 C14 BAD H 1 51.466 68.651 156.987 1.00 0.00 xxxx 2421 HETATM 2422 C16 BAD H 1 52.094 70.021 156.829 1.00 0.00 xxxx 2422 HETATM 2423 C11 BAD H 1 50.739 68.277 158.271 1.00 0.00 xxxx 2423 HETATM 2424 C12 BAD H 1 50.660 66.933 158.631 1.00 0.00 xxxx 2424 HETATM 2425 C13 BAD H 1 49.986 66.561 159.786 1.00 0.00 xxxx 2425 HETATM 2426 CO6 BAD H 1 49.377 67.558 160.602 1.00 0.00 xxxx 2426 HETATM 2427 CO5 BAD H 1 48.690 67.166 161.789 1.00 0.00 xxxx 2427 HETATM 2428 CIO BAD H 1 50.147 69.261 159.061 1.00 0.00 xxxx 2428 HETATM 2429 CO7 BAD H 1 49.452 68.876 160.251 1.00 0.00 xxxx 2429 HETATM 2430 CO8 BAD H 1 48.834 69.859 161.081 1.00 0.00 xxxx 2430 HETATM 2431 CO9 BAD H 1 48.162 69.475 162.242 1.00 0.00 xxxx 2431 HETATM 2432 CO4 BAD H 1 48.091 68.125 162.599 1.00 0.00 xxxx 2432 HETATM 2433 NO2 BAD H 1 47.388 67.716 163.803 1.00 0.00 xxxx 2433 HETATM 2434 CO3 BAD H 1 47.290 66.305 164.145 1.00 0.00 xxxx 2434 HETATM 2435 CO1 BAD H 1 46.768 68.713 164.659 1.00 0.00 xxxx 2435 HETATM 2436 O HOH S 1 46.201 68.225 153.472 1.00 0.00 xxxx 2436 HETATM 2437 O HOH S 2 57.279 69.627 150.623 1.00 0.00 xxxx 2437 HETATM 2438 O HOH S 3 58.043 66.399 149.833 1.00 0.00 xxxx 2438 HETATM 2439 O HOH S 4 66.517 72.086 144.915 1.00 0.00 xxxx 2439 HETATM 2440 O HOH S 5 57.929 64.558 156.347 1.00 0.00 xxxx 2440 HETATM 2441 O HOH S 6 37.622 49.306 143.693 1.00 0.00 xxxx 2441 HETATM 2442 O HOH S 7 56.704 54.067 156.413 1.00 0.00 xxxx 2442 HETATM 2443 O HOH S 8 46.778 48.831 152.298 1.00 0.00 xxxx 2443 HETATM 2444 O HOH S 9 30.024 63.081 131.116 1.00 0.00 xxxx 2444 HETATM 2445 O HOH S 10 36.187 49.751 136.009 1.00 0.00 xxxx 2445 HETATM 2446 O HOH S 11 48.055 42.688 150.299 1.00 0.00 xxxx 2446 HETATM 2447 O HOH S 12 51.905 91.444 154.694 1.00 0.00 xxxx 2447 HETATM 2448 O HOH S 13 74.040 77.495 151.343 1.00 0.00 xxxx 2448 HETATM 2449 O HOH S 14 47.118 71.039 153.130 1.00 0.00 xxxx 2449 HETATM 2450 O HOH S 15 49.393 92.404 147.572 1.00 0.00 xxxx 2450 HETATM 2451 O HOH S 16 51.139 49.072 152.311 1.00 0.00 xxxx 2451 HETATM 2452 O HOH S 17 49.392 60.954 144.600 1.00 0.00 xxxx 2452 HETATM 2453 O HOH S 18 57.680 96.227 150.341 1.00 0.00 xxxx 2453 HETATM 2454 O HOH S 19 29.378 63.519 143.831 1.00 0.00 xxxx 2454 HETATM 2455 O HOH S 20 64.108 78.535 142.366 1.00 0.00 xxxx 2455 HETATM 2456 O HOH S 21 43.239 51.830 156.655 1.00 0.00 xxxx 2456 HETATM 2457 O HOH S 22 39.137 53.223 153.258 1.00 0.00 xxxx 2457 HETATM 2458 O HOH S 23 40.641 53.517 156.840 1.00 0.00 xxxx 2458 HETATM 2459 O HOH S 24 75.860 67.970 153.435 1.00 0.00 xxxx 2459 HETATM 2460 O HOH S 25 60.885 68.326 148.044 1.00 0.00 xxxx 2460 HETATM 2461 O HOH S 26 56.455 69.597 153.366 1.00 0.00 xxxx 2461 HETATM 2462 O HOH S 27 49.093 78.034 156.339 1.00 0.00 xxxx 2462 HETATM 2463 O HOH S 28 51.534 84.253 141.942 1.00 0.00 xxxx 2463 HETATM 2464 O HOH S 29 41.409 72.967 151.410 1.00 0.00 xxxx 2464 HETATM 2465 O HOH S 30 52.391 92.584 150.793 1.00 0.00 xxxx 2465 HETATM 2466 O HOH S 31 49.882 88.636 156.756 1.00 0.00 xxxx 2466 HETATM 2467 O HOH S 32 49.907 49.386 133.465 1.00 0.00 xxxx 2467 HETATM 2468 O HOH S 33 51.656 93.752 148.385 1.00 0.00 xxxx 2468 HETATM 2469 O HOH S 34 46.499 77.583 143.348 1.00 0.00 xxxx 2469 HETATM 2470 O HOH S 35 47.019 43.680 137.225 1.00 0.00 xxxx 2470 HETATM 2471 O HOH S 36 62.183 62.671 153.207 1.00 0.00 xxxx 2471 HETATM 2472 O HOH S 37 54.270 92.901 154.716 1.00 0.00 xxxx 2472 HETATM 2473 O HOH S 38 54.221 63.904 137.446 1.00 0.00 xxxx 2473 HETATM 2474 O HOH S 39 41.749 75.482 143.484 1.00 0.00 xxxx 2474 HETATM 2475 O HOH S 40 38.789 74.147 149.924 1.00 0.00 xxxx 2475 HETATM 2476 O HOH S 41 57.442 50.553 153.136 1.00 0.00 xxxx 2476 HETATM 2477 O HOH S 42 45.951 75.220 138.761 1.00 0.00 xxxx 2477 HETATM 2478 O HOH S 43 38.706 67.514 135.380 1.00 0.00 xxxx 2478 HETATM 2479 O HOH S 44 68.866 91.816 177.553 1.00 0.00 xxxx 2479 HETATM 2480 O HOH S 45 50.702 42.893 149.907 1.00 0.00 xxxx 2480 HETATM 2481 O HOH S 46 74.261 65.933 144.734 1.00 0.00 xxxx 2481 HETATM 2482 O HOH S 47 55.766 48.358 144.532 1.00 0.00 xxxx 2482 HETATM 2483 O HOH S 48 54.068 47.601 151.452 1.00 0.00 xxxx 2483 HETATM 2484 O HOH S 49 36.924 48.495 146.281 1.00 0.00 xxxx 2484 HETATM 2485 O HOH S 50 28.577 63.305 141.186 1.00 0.00 xxxx 2485 HETATM 2486 O HOH S 51 56.380 51.624 155.427 1.00 0.00 xxxx 2486 HETATM 2487 O HOH S 52 46.843 76.105 147.173 1.00 0.00 xxxx 2487 HETATM 2488 O HOH S 53 54.201 94.196 152.355 1.00 0.00 xxxx 2488 HETATM 2489 O HOH S 54 36.411 66.940 136.708 1.00 0.00 xxxx 2489 HETATM 2490 O HOH S 55 34.508 64.230 133.579 1.00 0.00 xxxx 2490 HETATM 2491 O HOH S 56 37.469 75.613 143.245 1.00 0.00 xxxx 2491 HETATM 2492 O HOH S 57 41.259 63.933 132.633 1.00 0.00 xxxx 2492 HETATM 2493 O HOH S 58 56.874 61.551 158.772 1.00 0.00 xxxx 2493 HETATM 2494 O HOH S 59 56.894 82.352 168.913 1.00 0.00 xxxx 2494 HETATM 2495 O HOH S 60 52.215 45.595 146.666 1.00 0.00 xxxx 2495 HETATM 2496 O HOH S 61 69.476 66.394 148.256 1.00 0.00 xxxx 2496 HETATM 2497 O HOH S 62 44.078 67.855 155.344 1.00 0.00 xxxx 2497 HETATM 2498 O HOH S 63 37.822 64.070 158.296 1.00 0.00 xxxx 2498 HETATM 2499 O HOH S 64 31.238 72.940 145.995 1.00 0.00 xxxx 2499 HETATM 2500 O HOH S 65 58.159 86.918 140.884 1.00 0.00 xxxx 2500 HETATM 2501 O HOH S 66 31.369 69.344 139.912 1.00 0.00 xxxx 2501 HETATM 2502 O HOH S 67 75.699 79.234 155.569 1.00 0.00 xxxx 2502 HETATM 2503 O HOH S 68 74.962 66.801 158.209 1.00 0.00 xxxx 2503 HETATM 2504 O HOH S 69 61.668 65.708 146.688 1.00 0.00 xxxx 2504 HETATM 2505 O HOH S 70 47.651 39.922 149.628 1.00 0.00 xxxx 2505 HETATM 2506 O HOH S 71 50.222 79.601 143.279 1.00 0.00 xxxx 2506 HETATM 2507 O HOH S 72 36.280 50.638 133.281 1.00 0.00 xxxx 2507 HETATM 2508 O HOH S 73 56.688 91.754 155.167 1.00 0.00 xxxx 2508 HETATM 2509 O HOH S 74 56.515 91.297 141.991 1.00 0.00 xxxx 2509 HETATM 2510 O HOH S 75 60.126 97.716 151.243 1.00 0.00 xxxx 2510 HETATM 2511 O HOH S 76 59.113 72.275 155.191 1.00 0.00 xxxx 2511 HETATM 2512 O HOH S 77 39.286 65.407 133.676 1.00 0.00 xxxx 2512 HETATM 2513 O HOH S 78 51.850 77.610 168.352 1.00 0.00 xxxx 2513 HETATM 2514 O HOH S 79 63.904 96.103 150.019 1.00 0.00 xxxx 2514 HETATM 2515 O HOH S 80 30.586 65.593 134.386 1.00 0.00 xxxx 2515 HETATM 2516 O HOH S 81 42.210 63.701 164.172 1.00 0.00 xxxx 2516 HETATM 2517 O HOH S 82 58.490 52.146 143.356 1.00 0.00 xxxx 2517 HETATM 2518 O HOH S 83 35.827 64.052 153.949 1.00 0.00 xxxx 2518 HETATM 2519 O HOH S 84 51.916 66.901 138.432 1.00 0.00 xxxx 2519 HETATM 2520 O HOH S 85 45.093 72.744 152.280 1.00 0.00 xxxx 2520 HETATM 2521 O HOH S 86 55.336 96.534 151.494 1.00 0.00 xxxx 2521 HETATM 2522 O HOH S 87 54.897 53.328 158.820 1.00 0.00 xxxx 2522 HETATM 2523 O HOH S 88 51.214 76.347 140.158 1.00 0.00 xxxx 2523 HETATM 2524 O HOH S 89 76.016 74.651 156.563 1.00 0.00 xxxx 2524 HETATM 2525 O HOH S 90 76.998 77.686 147.743 1.00 0.00 xxxx 2525 HETATM 2526 O HOH S 91 45.905 86.694 146.512 1.00 0.00 xxxx 2526 HETATM 2527 O HOH S 92 49.430 92.090 144.568 1.00 0.00 xxxx 2527 HETATM 2528 O HOH S 93 39.674 61.796 131.497 1.00 0.00 xxxx 2528 HETATM 2529 O HOH S 94 55.245 99.007 153.139 1.00 0.00 xxxx 2529 HETATM 2530 O HOH S 95 69.244 63.350 148.315 1.00 0.00 xxxx 2530 HETATM 2531 O HOH S 96 62.369 67.500 144.662 1.00 0.00 xxxx 2531 HETATM 2532 O HOH S 97 51.637 42.869 152.661 1.00 0.00 xxxx 2532 HETATM 2533 O HOH S 98 53.212 61.591 136.064 1.00 0.00 xxxx 2533 HETATM 2534 O HOH S 99 66.212 62.210 156.589 1.00 0.00 xxxx 2534 HETATM 2535 O HOH S 100 35.206 69.485 136.668 1.00 0.00 xxxx 2535 HETATM 2536 O HOH S 101 67.877 74.242 138.545 1.00 0.00 xxxx 2536 HETATM 2537 O HOH S 102 47.256 88.958 147.564 1.00 0.00 xxxx 2537 HETATM 2538 O HOH S 103 48.802 89.549 152.888 1.00 0.00 xxxx 2538 HETATM 2539 O HOH S 104 55.533 47.093 149.026 1.00 0.00 xxxx 2539 HETATM 2540 O HOH S 105 58.683 84.568 172.531 1.00 0.00 xxxx 2540 HETATM 2541 O HOH S 106 46.755 54.806 131.997 1.00 0.00 xxxx 2541 HETATM 2542 O HOH S 107 79.055 76.628 162.628 1.00 0.00 xxxx 2542 HETATM 2543 O HOH S 108 35.822 74.142 141.537 1.00 0.00 xxxx 2543 HETATM 2544 O HOH S 109 50.310 81.760 142.022 1.00 0.00 xxxx 2544 HETATM 2545 O HOH S 110 63.805 83.471 140.207 1.00 0.00 xxxx 2545 HETATM 2546 O HOH S 111 27.119 60.930 140.514 1.00 0.00 xxxx 2546 HETATM 2547 O HOH S 112 57.702 49.618 146.404 1.00 0.00 xxxx 2547 HETATM 2548 O HOH S 113 53.156 41.009 142.253 1.00 0.00 xxxx 2548 HETATM 2549 O HOH S 114 60.853 82.005 137.338 1.00 0.00 xxxx 2549 HETATM 2550 O HOH S 115 65.759 67.945 145.250 1.00 0.00 xxxx 2550 HETATM 2551 O HOH S 116 79.693 79.535 162.418 1.00 0.00 xxxx 2551 HETATM 2552 O HOH S 117 42.135 47.615 154.138 1.00 0.00 xxxx 2552 HETATM 2553 O HOH S 118 57.040 63.514 136.108 1.00 0.00 xxxx 2553 HETATM 2554 O HOH S 119 31.769 48.527 146.542 1.00 0.00 xxxx 2554 HETATM 2555 O HOH S 120 57.039 84.513 139.915 1.00 0.00 xxxx 2555 HETATM 2556 O HOH S 121 46.159 42.652 139.578 1.00 0.00 xxxx 2556 HETATM 2557 O HOH S 122 53.925 44.527 149.407 1.00 0.00 xxxx 2557 HETATM 2558 O HOH S 123 66.892 67.604 166.801 1.00 0.00 xxxx 2558 HETATM 2559 O HOH S 124 35.159 66.646 134.153 1.00 0.00 xxxx 2559 HETATM 2560 O HOH S 125 78.744 72.675 165.106 1.00 0.00 xxxx 2560 HETATM 2561 O HOH S 126 76.832 75.603 145.788 1.00 0.00 xxxx 2561 HETATM 2562 O HOH S 127 54.214 57.362 136.743 1.00 0.00 xxxx 2562 HETATM 2563 O HOH S 128 53.898 47.656 146.752 1.00 0.00 xxxx 2563 HETATM 2564 O HOH S 129 49.728 63.948 162.353 1.00 0.00 xxxx 2564 HETATM 2565 O HOH S 130 57.315 85.289 167.511 1.00 0.00 xxxx 2565 HETATM 2566 O HOH S 131 72.797 63.380 153.609 1.00 0.00 xxxx 2566 HETATM 2567 O HOH S 132 55.428 92.803 143.759 1.00 0.00 xxxx 2567 HETATM 2568 O HOH S 133 68.279 93.604 148.640 1.00 0.00 xxxx 2568 HETATM 2569 O HOH S 134 76.091 89.391 150.922 1.00 0.00 xxxx 2569 HETATM 2570 O HOH S 135 45.377 74.405 150.380 1.00 0.00 xxxx 2570 HETATM 2571 O HOH S 136 44.404 77.789 145.325 1.00 0.00 xxxx 2571 HETATM 2572 O HOH S 137 45.325 74.050 136.311 1.00 0.00 xxxx 2572 HETATM 2573 O HOH S 138 73.690 79.101 140.386 1.00 0.00 xxxx 2573 HETATM 2574 O HOH S 139 52.155 93.059 144.447 1.00 0.00 xxxx 2574 HETATM 2575 O HOH S 140 40.016 69.933 155.465 1.00 0.00 xxxx 2575 HETATM 2576 O HOH S 141 50.687 90.990 157.036 1.00 0.00 xxxx 2576 HETATM 2577 O HOH S 142 32.692 60.138 157.561 1.00 0.00 xxxx 2577 HETATM 2578 O HOH S 143 37.136 46.283 149.886 1.00 0.00 xxxx 2578 HETATM 2579 O HOH S 144 64.760 94.189 148.540 1.00 0.00 xxxx 2579 HETATM 2580 O HOH S 145 44.949 83.318 153.400 1.00 0.00 xxxx 2580 HETATM 2581 O HOH S 146 49.102 45.603 154.088 1.00 0.00 xxxx 2581 HETATM 2582 O HOH S 147 50.741 82.205 161.982 1.00 0.00 xxxx 2582 HETATM 2583 O HOH S 148 45.534 91.850 151.024 1.00 0.00 xxxx 2583 HETATM 2584 O HOH S 149 26.998 57.738 151.095 1.00 0.00 xxxx 2584 HETATM 2585 O HOH S 150 57.998 96.596 147.563 1.00 0.00 xxxx 2585 HETATM 2586 O HOH S 151 54.046 55.078 135.707 1.00 0.00 xxxx 2586 HETATM 2587 O HOH S 152 36.107 62.034 158.248 1.00 0.00 xxxx 2587 HETATM 2588 O HOH S 153 69.880 93.089 164.909 1.00 0.00 xxxx 2588 HETATM 2589 O HOH S 154 44.962 55.765 130.418 1.00 0.00 xxxx 2589 HETATM 2590 O HOH S 155 69.382 76.162 166.572 1.00 0.00 xxxx 2590 HETATM 2591 O HOH S 156 48.993 48.521 153.991 1.00 0.00 xxxx 2591 HETATM 2592 O HOH S 157 42.538 75.186 150.705 1.00 0.00 xxxx 2592 HETATM 2593 O HOH S 158 34.529 47.526 131.504 1.00 0.00 xxxx 2593 HETATM 2594 O HOH S 159 68.597 95.583 154.648 1.00 0.00 xxxx 2594 HETATM 2595 O HOH S 160 47.611 89.569 155.230 1.00 0.00 xxxx 2595 HETATM 2596 O HOH S 161 41.586 43.733 142.934 1.00 0.00 xxxx 2596 HETATM 2597 O HOH S 162 67.759 84.003 171.737 1.00 0.00 xxxx 2597 HETATM 2598 O HOH S 163 34.711 71.043 138.594 1.00 0.00 xxxx 2598 HETATM 2599 O HOH S 164 32.185 67.192 133.433 1.00 0.00 xxxx 2599 HETATM 2600 O HOH S 165 64.999 65.696 145.876 1.00 0.00 xxxx 2600 HETATM 2601 O HOH S 166 56.782 64.948 164.863 1.00 0.00 xxxx 2601 HETATM 2602 O HOH S 167 72.553 89.540 144.762 1.00 0.00 xxxx 2602 HETATM 2603 O HOH S 168 53.053 66.089 136.571 1.00 0.00 xxxx 2603 HETATM 2604 O HOH S 169 52.271 72.917 167.041 1.00 0.00 xxxx 2604 HETATM 2605 O HOH S 170 70.989 61.973 155.873 1.00 0.00 xxxx 2605 HETATM 2606 O HOH S 171 48.753 73.251 164.610 1.00 0.00 xxxx 2606 HETATM 2607 O HOH S 172 51.477 45.150 153.501 1.00 0.00 xxxx 2607 HETATM 2608 O HOH S 173 70.613 93.728 160.943 1.00 0.00 xxxx 2608 HETATM 2609 O HOH S 174 51.891 92.250 158.877 1.00 0.00 xxxx 2609 HETATM 2610 O HOH S 175 48.940 42.197 136.314 1.00 0.00 xxxx 2610 HETATM 2611 O HOH S 176 68.735 63.111 155.715 1.00 0.00 xxxx 2611 HETATM 2612 O HOH S 177 60.769 62.992 166.104 1.00 0.00 xxxx 2612 HETATM 2613 O HOH S 178 50.187 93.478 153.677 1.00 0.00 xxxx 2613 HETATM 2614 O HOH S 179 51.213 80.674 164.196 1.00 0.00 xxxx 2614 HETATM 2615 O HOH S 180 49.537 49.269 156.623 1.00 0.00 xxxx 2615 HETATM 2616 O HOH S 181 77.139 80.622 157.215 1.00 0.00 xxxx 2616 HETATM 2617 O HOH S 182 71.895 90.577 158.371 1.00 0.00 xxxx 2617 HETATM 2618 O HOH S 183 49.979 79.111 167.457 1.00 0.00 xxxx 2618 HETATM 2619 O HOH S 184 39.460 72.232 154.081 1.00 0.00 xxxx 2619 HETATM 2620 O HOH S 185 57.704 47.790 153.481 1.00 0.00 xxxx 2620 HETATM 2621 O HOH S 186 36.677 72.491 139.643 1.00 0.00 xxxx 2621 HETATM 2622 O HOH S 187 71.999 61.960 151.927 1.00 0.00 xxxx 2622 HETATM 2623 O HOH S 188 47.075 72.908 162.806 1.00 0.00 xxxx 2623 HETATM 2624 O HOH S 189 35.414 76.807 144.818 1.00 0.00 xxxx 2624 HETATM 2625 O HOH S 190 78.789 76.672 149.395 1.00 0.00 xxxx 2625 HETATM 2626 O HOH S 191 60.444 53.912 142.416 1.00 0.00 xxxx 2626 HETATM 2627 O HOH S 192 42.137 43.424 130.368 1.00 0.00 xxxx 2627 HETATM 2628 O HOH S 193 40.114 41.774 129.906 1.00 0.00 xxxx 2628 HETATM 2629 O HOH S 194 60.042 77.391 172.458 1.00 0.00 xxxx 2629 HETATM 2630 O HOH S 195 58.805 47.855 156.024 1.00 0.00 xxxx 2630 HETATM 2631 O HOH S 196 60.005 50.731 150.338 1.00 0.00 xxxx 2631 HETATM 2632 O HOH S 197 59.841 61.910 160.341 1.00 0.00 xxxx 2632 HETATM 2633 O HOH S 198 77.400 74.129 149.989 1.00 0.00 xxxx 2633 HETATM 2634 O HOH S 199 53.896 98.937 155.309 1.00 0.00 xxxx 2634 HETATM 2635 O HOH S 200 59.636 83.798 138.796 1.00 0.00 xxxx 2635 HETATM 2636 O HOH S 201 32.247 43.843 140.408 1.00 0.00 xxxx 2636 HETATM 2637 O HOH S 202 29.486 64.466 155.083 1.00 0.00 xxxx 2637 HETATM 2638 O HOH S 203 42.716 72.150 135.089 1.00 0.00 xxxx 2638 HETATM 2639 O HOH S 204 71.987 88.136 159.671 1.00 0.00 xxxx 2639 HETATM 2640 O HOH S 205 33.381 49.010 136.893 1.00 0.00 xxxx 2640 HETATM 2641 O HOH S 206 69.194 95.620 149.891 1.00 0.00 xxxx 2641 HETATM 2642 O HOH S 207 29.387 55.844 141.016 1.00 0.00 xxxx 2642 HETATM 2643 O HOH S 208 45.490 92.898 153.531 1.00 0.00 xxxx 2643 HETATM 2644 O HOH S 209 78.479 75.596 143.871 1.00 0.00 xxxx 2644 HETATM 2645 O HOH S 210 54.709 51.509 162.804 1.00 0.00 xxxx 2645 HETATM 2646 O HOH S 211 48.561 89.863 144.071 1.00 0.00 xxxx 2646 HETATM 2647 O HOH S 212 39.863 48.853 153.284 1.00 0.00 xxxx 2647 HETATM 2648 O HOH S 213 80.062 74.843 164.569 1.00 0.00 xxxx 2648 HETATM 2649 O HOH S 214 38.835 54.728 150.936 1.00 0.00 xxxx 2649 HETATM 2650 O HOH S 215 68.967 65.864 155.242 1.00 0.00 xxxx 2650 HETATM 2651 O HOH S 216 68.172 67.122 145.858 1.00 0.00 xxxx 2651 HETATM 2652 O HOH S 217 68.298 64.720 144.670 1.00 0.00 xxxx 2652 HETATM 2653 O HOH S 218 71.593 72.342 144.610 1.00 0.00 xxxx 2653 HETATM 2654 O HOH S 219 64.396 61.473 153.855 1.00 0.00 xxxx 2654 HETATM 2655 O HOH S 220 55.312 96.339 144.330 1.00 0.00 xxxx 2655 HETATM 2656 O HOH S 221 54.183 48.804 155.351 1.00 0.00 xxxx 2656 HETATM 2657 O HOH S 222 74.731 90.692 145.593 1.00 0.00 xxxx 2657 HETATM 2658 O HOH S 223 37.467 65.926 160.398 1.00 0.00 xxxx 2658 HETATM 2659 O HOH S 224 27.727 58.401 140.473 1.00 0.00 xxxx 2659 HETATM 2660 O HOH S 225 43.576 85.936 150.480 1.00 0.00 xxxx 2660 HETATM 2661 O HOH S 226 45.728 86.581 156.293 1.00 0.00 xxxx 2661 HETATM 2662 O HOH S 227 49.995 92.055 151.996 1.00 0.00 xxxx 2662 HETATM 2663 O HOH S 228 37.499 47.113 152.538 1.00 0.00 xxxx 2663 HETATM 2664 O HOH S 229 44.424 61.222 132.009 1.00 0.00 xxxx 2664 HETATM 2665 O HOH S 230 76.652 68.937 159.384 1.00 0.00 xxxx 2665 HETATM 2666 O HOH S 231 40.922 61.562 164.902 1.00 0.00 xxxx 2666 HETATM 2667 O HOH S 232 64.719 94.729 167.844 1.00 0.00 xxxx 2667 HETATM 2668 O HOH S 233 43.542 59.604 131.071 1.00 0.00 xxxx 2668 HETATM 2669 O HOH S 234 51.200 63.892 135.249 1.00 0.00 xxxx 2669 HETATM 2670 O HOH S 235 55.405 91.022 139.852 1.00 0.00 xxxx 2670 HETATM 2671 O HOH S 236 40.342 65.511 164.886 1.00 0.00 xxxx 2671 HETATM 2672 O HOH S 237 66.483 99.541 155.727 1.00 0.00 xxxx 2672 HETATM 2673 O HOH S 238 69.457 86.310 171.372 1.00 0.00 xxxx 2673 HETATM 2674 O HOH S 239 44.207 49.050 155.766 1.00 0.00 xxxx 2674 HETATM 2675 O HOH S 240 77.984 88.107 149.281 1.00 0.00 xxxx 2675 HETATM 2676 O HOH S 241 63.936 65.431 143.959 1.00 0.00 xxxx 2676 HETATM 2677 O HOH S 242 59.342 56.830 138.270 1.00 0.00 xxxx 2677 HETATM 2678 O HOH S 243 57.960 56.896 136.242 1.00 0.00 xxxx 2678 HETATM 2679 O HOH S 244 58.013 47.012 148.836 1.00 0.00 xxxx 2679 HETATM 2680 O HOH S 245 75.427 69.810 142.388 1.00 0.00 xxxx 2680 HETATM 2681 O HOH S 246 73.826 68.223 143.334 1.00 0.00 xxxx 2681 HETATM 2682 O HOH S 247 42.971 82.759 155.019 1.00 0.00 xxxx 2682 HETATM 2683 O HOH S 248 52.571 85.235 164.090 1.00 0.00 xxxx 2683 HETATM 2684 O HOH S 249 45.214 46.605 152.420 1.00 0.00 xxxx 2684 HETATM 2685 O HOH S 250 29.343 67.140 135.830 1.00 0.00 xxxx 2685 HETATM 2686 O HOH S 251 32.366 55.742 159.321 1.00 0.00 xxxx 2686 HETATM 2687 O HOH S 252 24.677 53.488 148.443 1.00 0.00 xxxx 2687 HETATM 2688 O HOH S 253 53.247 94.555 156.841 1.00 0.00 xxxx 2688 HETATM 2689 O HOH S 254 74.994 84.859 143.239 1.00 0.00 xxxx 2689 HETATM 2690 O HOH S 255 42.936 91.602 150.830 1.00 0.00 xxxx 2690 HETATM 2691 O HOH S 256 58.422 83.991 169.629 1.00 0.00 xxxx 2691 HETATM 2692 O HOH S 257 69.838 92.467 158.698 1.00 0.00 xxxx 2692 HETATM 2693 O HOH S 258 68.045 85.333 139.314 1.00 0.00 xxxx 2693 HETATM 2694 O HOH S 259 60.263 52.077 139.361 1.00 0.00 xxxx 2694 HETATM 2695 O HOH S 260 27.165 65.538 140.881 1.00 0.00 xxxx 2695 HETATM 2696 O HOH S 261 64.093 93.917 162.579 1.00 0.00 xxxx 2696 HETATM 2697 O HOH S 262 58.261 93.702 145.184 1.00 0.00 xxxx 2697 HETATM 2698 O HOH S 263 43.274 41.321 143.716 1.00 0.00 xxxx 2698 HETATM 2699 O HOH S 264 44.457 63.916 165.291 1.00 0.00 xxxx 2699 HETATM 2700 O HOH S 265 42.371 41.840 141.713 1.00 0.00 xxxx 2700 HETATM 2701 O HOH S 266 32.912 69.796 134.996 1.00 0.00 xxxx 2701 HETATM 2702 O HOH S 267 38.574 62.379 129.054 1.00 0.00 xxxx 2702 HETATM 2703 O HOH S 268 52.919 55.185 167.684 1.00 0.00 xxxx 2703 HETATM 2704 O HOH S 269 42.297 73.045 138.008 1.00 0.00 xxxx 2704 HETATM 2705 O HOH S 270 55.678 97.395 147.147 1.00 0.00 xxxx 2705 HETATM 2706 O HOH S 271 52.073 77.661 142.443 1.00 0.00 xxxx 2706 HETATM 2707 O HOH S 272 53.656 79.318 140.562 1.00 0.00 xxxx 2707 HETATM 2708 O HOH S 273 46.237 72.352 160.290 1.00 0.00 xxxx 2708 HETATM 2709 O HOH S 274 46.994 92.936 143.057 1.00 0.00 xxxx 2709 HETATM 2710 O HOH S 275 44.477 81.823 145.212 1.00 0.00 xxxx 2710 HETATM 2711 O HOH S 276 54.031 87.747 163.437 1.00 0.00 xxxx 2711 HETATM 2712 O HOH S 277 47.434 52.681 166.283 1.00 0.00 xxxx 2712 HETATM 2713 O HOH S 278 59.600 57.004 158.284 1.00 0.00 xxxx 2713 HETATM 2714 O HOH S 279 60.963 54.848 139.584 1.00 0.00 xxxx 2714 HETATM 2715 O HOH S 280 37.148 63.959 132.391 1.00 0.00 xxxx 2715 HETATM 2716 O HOH S 281 28.986 71.953 146.829 1.00 0.00 xxxx 2716 HETATM 2717 O HOH S 282 68.512 94.290 162.575 1.00 0.00 xxxx 2717 HETATM 2718 O HOH S 283 52.234 40.696 137.518 1.00 0.00 xxxx 2718 HETATM 2719 O HOH S 284 66.206 85.004 174.135 1.00 0.00 xxxx 2719 HETATM 2720 O HOH S 285 75.905 76.142 152.137 1.00 0.00 xxxx 2720 HETATM 2721 O HOH S 286 50.731 54.152 132.775 1.00 0.00 xxxx 2721 HETATM 2722 O HOH S 287 54.504 71.995 168.294 1.00 0.00 xxxx 2722 HETATM 2723 O HOH S 288 56.248 96.171 141.897 1.00 0.00 xxxx 2723 HETATM 2724 O HOH S 289 69.486 62.152 150.746 1.00 0.00 xxxx 2724 HETATM 2725 O HOH S 290 40.024 40.276 140.882 1.00 0.00 xxxx 2725 HETATM 2726 O HOH S 291 44.385 41.941 132.405 1.00 0.00 xxxx 2726 HETATM 2727 O HOH S 292 71.883 78.785 169.503 1.00 0.00 xxxx 2727 HETATM 2728 O HOH S 293 56.087 94.966 139.562 1.00 0.00 xxxx 2728 HETATM 2729 O HOH S 294 50.604 86.542 161.142 1.00 0.00 xxxx 2729 HETATM 2730 O HOH S 295 49.091 55.663 133.859 1.00 0.00 xxxx 2730 HETATM 2731 O HOH S 296 62.140 68.428 142.203 1.00 0.00 xxxx 2731 HETATM 2732 O HOH S 297 58.188 60.998 161.107 1.00 0.00 xxxx 2732 HETATM 2733 O HOH S 298 34.634 46.282 149.220 1.00 0.00 xxxx 2733 HETATM 2734 O HOH S 299 53.105 97.360 156.777 1.00 0.00 xxxx 2734 HETATM 2735 O HOH S 300 23.462 59.601 146.117 1.00 0.00 xxxx 2735 HETATM 2736 O HOH S 301 55.964 92.355 162.949 1.00 0.00 xxxx 2736 HETATM 2737 O HOH S 302 27.393 66.398 134.317 1.00 0.00 xxxx 2737 HETATM 2738 O HOH S 303 61.386 88.815 145.169 1.00 0.00 xxxx 2738 HETATM 2739 O HOH S 304 51.190 51.469 157.598 1.00 0.00 xxxx 2739 HETATM 2740 O HOH S 305 25.996 59.783 135.372 1.00 0.00 xxxx 2740 HETATM 2741 O HOH S 306 33.722 43.191 142.370 1.00 0.00 xxxx 2741 HETATM 2742 O HOH S 307 42.824 79.527 144.482 1.00 0.00 xxxx 2742 HETATM 2743 O HOH S 308 46.683 73.714 134.659 1.00 0.00 xxxx 2743 HETATM 2744 O HOH S 309 39.500 50.446 155.833 1.00 0.00 xxxx 2744 HETATM 2745 O HOH S 310 55.858 87.737 140.514 1.00 0.00 xxxx 2745 HETATM 2746 O HOH S 311 51.193 56.462 133.700 1.00 0.00 xxxx 2746 HETATM 2747 O HOH S 312 59.165 45.441 139.785 1.00 0.00 xxxx 2747 HETATM 2748 O HOH S 313 53.333 78.458 170.965 1.00 0.00 xxxx 2748 HETATM 2749 O HOH S 314 49.285 85.987 141.326 1.00 0.00 xxxx 2749 HETATM 2750 O HOH S 315 35.185 60.851 156.183 1.00 0.00 xxxx 2750 HETATM 2751 O HOH S 316 75.105 83.783 158.857 1.00 0.00 xxxx 2751 HETATM 2752 O HOH S 317 64.272 59.277 147.662 1.00 0.00 xxxx 2752 HETATM 2753 O HOH S 318 77.413 76.276 140.638 1.00 0.00 xxxx 2753 HETATM 2754 O HOH S 319 76.605 82.256 158.647 1.00 0.00 xxxx 2754 HETATM 2755 O HOH S 320 29.536 56.236 132.756 1.00 0.00 xxxx 2755 HETATM 2756 O HOH S 321 78.091 77.379 142.155 1.00 0.00 xxxx 2756 HETATM 2757 O HOH S 322 59.988 69.316 150.305 1.00 0.00 xxxx 2757 HETATM 2758 O HOH S 323 52.661 46.359 135.892 1.00 0.00 xxxx 2758 HETATM 2759 O HOH S 324 34.321 47.279 146.428 1.00 0.00 xxxx 2759 HETATM 2760 O HOH S 325 75.579 93.207 168.490 1.00 0.00 xxxx 2760 HETATM 2761 O HOH S 326 43.288 63.060 132.086 1.00 0.00 xxxx 2761 HETATM 2762 O HOH S 327 66.171 97.517 150.411 1.00 0.00 xxxx 2762 HETATM 2763 O HOH S 328 31.253 56.201 131.353 1.00 0.00 xxxx 2763 HETATM 2764 O HOH S 329 45.863 41.542 134.212 1.00 0.00 xxxx 2764 HETATM 2765 O HOH S 330 51.530 72.106 164.595 1.00 0.00 xxxx 2765 HETATM 2766 O HOH S 331 57.118 92.826 158.098 1.00 0.00 xxxx 2766 HETATM 2767 O HOH S 332 60.186 54.769 150.237 1.00 0.00 xxxx 2767 HETATM 2768 O HOH S 333 77.624 72.381 139.249 1.00 0.00 xxxx 2768 HETATM 2769 O HOH S 334 45.538 77.271 164.125 1.00 0.00 xxxx 2769 HETATM 2770 O HOH S 335 25.140 65.377 135.730 1.00 0.00 xxxx 2770 HETATM 2771 O HOH S 336 74.824 77.536 168.183 1.00 0.00 xxxx 2771 HETATM 2772 O HOH S 337 78.522 85.266 151.265 1.00 0.00 xxxx 2772 HETATM 2773 O HOH S 338 57.875 71.649 166.102 1.00 0.00 xxxx 2773 HETATM 2774 O HOH S 339 39.030 37.543 149.135 1.00 0.00 xxxx 2774 HETATM 2775 O HOH S 340 41.320 40.877 138.844 1.00 0.00 xxxx 2775 HETATM 2776 O HOH S 341 65.399 60.174 155.252 1.00 0.00 xxxx 2776 HETATM 2777 O HOH S 342 72.011 89.306 162.040 1.00 0.00 xxxx 2777 HETATM 2778 O HOH S 343 47.174 48.497 131.385 1.00 0.00 xxxx 2778 HETATM 2779 O HOH S 344 75.680 73.049 169.298 1.00 0.00 xxxx 2779 HETATM 2780 O HOH S 345 40.786 70.442 133.027 1.00 0.00 xxxx 2780 HETATM 2781 O HOH S 346 37.925 40.317 149.883 1.00 0.00 xxxx 2781 HETATM 2782 O HOH S 347 76.697 72.821 154.946 1.00 0.00 xxxx 2782 HETATM 2783 O HOH S 348 63.421 65.807 141.012 1.00 0.00 xxxx 2783 HETATM 2784 O HOH S 349 51.122 59.252 136.857 1.00 0.00 xxxx 2784 HETATM 2785 O HOH S 350 70.369 94.016 156.050 1.00 0.00 xxxx 2785 HETATM 2786 O HOH S 351 49.992 60.017 134.717 1.00 0.00 xxxx 2786 HETATM 2787 O HOH S 352 75.350 86.671 157.529 1.00 0.00 xxxx 2787 HETATM 2788 O HOH S 353 77.823 75.935 166.556 1.00 0.00 xxxx 2788 HETATM 2789 O HOH S 354 55.100 90.751 160.307 1.00 0.00 xxxx 2789 HETATM 2790 O HOH S 355 27.904 71.090 145.335 1.00 0.00 xxxx 2790 HETATM 2791 O HOH S 356 43.946 74.064 159.815 1.00 0.00 xxxx 2791 HETATM 2792 O HOH S 357 53.394 90.181 160.815 1.00 0.00 xxxx 2792 HETATM 2793 O HOH S 358 64.402 87.495 170.323 1.00 0.00 xxxx 2793 HETATM 2794 O HOH S 359 73.875 86.615 159.747 1.00 0.00 xxxx 2794 HETATM 2795 O HOH S 360 39.522 67.049 162.161 1.00 0.00 xxxx 2795 HETATM 2796 O HOH S 361 44.455 81.429 142.143 1.00 0.00 xxxx 2796 HETATM 2797 O HOH S 362 25.454 62.332 138.307 1.00 0.00 xxxx 2797 HETATM 2798 O HOH S 363 55.641 89.241 165.418 1.00 0.00 xxxx 2798 HETATM 2799 O HOH S 364 44.808 82.801 150.463 1.00 0.00 xxxx 2799 HETATM 2800 O HOH S 365 72.236 81.203 173.001 1.00 0.00 xxxx 2800 HETATM 2801 O HOH S 366 68.892 66.917 168.696 1.00 0.00 xxxx 2801 HETATM 2802 O HOH S 367 56.464 50.291 134.278 1.00 0.00 xxxx 2802 HETATM 2803 O HOH S 368 62.491 61.198 139.575 1.00 0.00 xxxx 2803 HETATM 2804 O HOH S 369 60.971 62.929 137.733 1.00 0.00 xxxx 2804 HETATM 2805 O HOH S 370 61.950 98.032 148.878 1.00 0.00 xxxx 2805 HETATM 2806 O HOH S 371 30.702 69.382 135.319 1.00 0.00 xxxx 2806 HETATM 2807 O HOH S 372 72.835 83.672 172.687 1.00 0.00 xxxx 2807 HETATM 2808 O HOH S 373 30.631 53.789 158.886 1.00 0.00 xxxx 2808 HETATM 2809 O HOH S 374 58.769 92.752 159.679 1.00 0.00 xxxx 2809 HETATM 2810 O HOH S 375 55.480 50.180 157.300 1.00 0.00 xxxx 2810 HETATM 2811 O HOH S 376 39.942 68.852 162.294 1.00 0.00 xxxx 2811 HETATM 2812 O HOH S 377 63.692 63.207 141.734 1.00 0.00 xxxx 2812 HETATM 2813 O HOH S 378 56.000 76.808 172.839 1.00 0.00 xxxx 2813 HETATM 2814 O HOH S 379 74.372 83.991 169.863 1.00 0.00 xxxx 2814 HETATM 2815 O HOH S 380 22.549 63.907 135.222 1.00 0.00 xxxx 2815 HETATM 2816 O HOH S 381 23.412 65.534 135.198 1.00 0.00 xxxx 2816 HETATM 2817 O HOH S 382 60.263 67.901 140.518 1.00 0.00 xxxx 2817 HETATM 2818 O HOH S 383 45.221 69.427 160.951 1.00 0.00 xxxx 2818 HETATM 2819 O HOH S 384 66.498 92.424 164.876 1.00 0.00 xxxx 2819 HETATM 2820 O HOH S 385 37.032 71.203 135.720 1.00 0.00 xxxx 2820 HETATM 2821 O HOH S 386 77.411 79.795 146.037 1.00 0.00 xxxx 2821 HETATM 2822 O HOH S 387 47.947 41.913 141.390 1.00 0.00 xxxx 2822 HETATM 2823 O HOH S 388 60.964 60.212 161.343 1.00 0.00 xxxx 2823 HETATM 2824 O HOH S 389 45.817 86.091 143.837 1.00 0.00 xxxx 2824 HETATM 2825 O HOH S 390 76.619 77.018 167.654 1.00 0.00 xxxx 2825 HETATM 2826 O HOH S 391 42.858 79.646 148.541 1.00 0.00 xxxx 2826 HETATM 2827 O HOH S 392 54.410 83.651 164.891 1.00 0.00 xxxx 2827 HETATM 2828 O HOH S 393 70.894 63.870 144.402 1.00 0.00 xxxx 2828 HETATM 2829 O HOH S 394 36.961 58.639 165.920 1.00 0.00 xxxx 2829 HETATM 2830 O HOH S 395 58.708 92.155 141.294 1.00 0.00 xxxx 2830 HETATM 2831 O HOH S 396 78.814 78.170 154.417 1.00 0.00 xxxx 2831 HETATM 2832 O HOH S 397 42.611 75.099 155.809 1.00 0.00 xxxx 2832 HETATM 2833 O HOH S 398 72.716 86.788 143.422 1.00 0.00 xxxx 2833 HETATM 2834 O HOH S 399 43.847 80.375 147.143 1.00 0.00 xxxx 2834 HETATM 2835 O HOH S 400 44.815 39.074 135.864 1.00 0.00 xxxx 2835 HETATM 2836 O HOH S 401 62.460 74.450 172.476 1.00 0.00 xxxx 2836 HETATM 2837 O HOH S 402 79.224 81.985 160.103 1.00 0.00 xxxx 2837 HETATM 2838 O HOH S 403 79.319 80.456 154.759 1.00 0.00 xxxx 2838

EXAMPLE 12 Crystal Structure Coordinates for a T. thermosaccharolyticum Glucose-Galactose Binding Protein: TTHGBP182C.ACRYLODAN (Acrylodan Attached to W182C Mutant+R91K,Q18E Double Mutant)

Naming is standard three-letter amino acid code.

For hetero atom (HETATM) records:

-   -   CA, calcium     -   HOH, water     -   ACR, Acrylodan     -   K, potassium     -   EDO, ethylene glycol

ATOM 1 O MET A 1 45.210 37.591 106.914 1.00 0.00 xxxx 1 ATOM 2 N MET A 1 45.762 36.296 109.277 1.00 0.00 xxxx 2 ATOM 3 CA MET A 1 46.329 35.790 108.035 1.00 0.00 xxxx 3 ATOM 4 C MET A 1 46.138 36.788 106.900 1.00 0.00 xxxx 4 ATOM 5 CB MET A 1 45.670 34.462 107.649 1.00 0.00 xxxx 5 ATOM 6 CG MET A 1 45.720 33.401 108.732 1.00 0.00 xxxx 6 ATOM 7 SD MET A 1 47.393 32.806 109.049 1.00 0.00 xxxx 7 ATOM 8 CE MET A 1 47.362 32.657 110.834 1.00 0.00 xxxx 8 ATOM 9 N LYS A 2 47.025 36.728 105.914 1.00 0.00 xxxx 9 ATOM 10 CA LYS A 2 46.833 37.493 104.692 1.00 0.00 xxxx 10 ATOM 11 C LYS A 2 45.651 36.919 103.923 1.00 0.00 xxxx 11 ATOM 12 O LYS A 2 45.477 35.699 103.844 1.00 0.00 xxxx 12 ATOM 13 CB LYS A 2 48.101 37.412 103.835 1.00 0.00 xxxx 13 ATOM 14 CG LYS A 2 48.098 38.337 102.634 1.00 0.00 xxxx 14 ATOM 15 CD LYS A 2 49.485 38.473 102.012 1.00 0.00 xxxx 15 ATOM 16 CE LYS A 2 49.883 37.224 101.251 1.00 0.00 xxxx 16 ATOM 17 NZ LYS A 2 51.165 37.424 100.517 1.00 0.00 xxxx 17 ATOM 18 N GLN A 3 44.819 37.797 103.364 1.00 0.00 xxxx 18 ATOM 19 CA GLN A 3 43.674 37.341 102.583 1.00 0.00 xxxx 19 ATOM 20 C GLN A 3 44.115 37.047 101.155 1.00 0.00 xxxx 20 ATOM 21 O GLN A 3 44.627 37.928 100.458 1.00 0.00 xxxx 21 ATOM 22 CB GLN A 3 42.546 38.370 102.593 1.00 0.00 xxxx 22 ATOM 23 CG GLN A 3 41.288 37.854 101.877 1.00 0.00 xxxx 23 ATOM 24 CD GLN A 3 40.152 38.869 101.821 1.00 0.00 xxxx 24 ATOM 25 OE1 GLN A 3 40.188 39.812 101.033 1.00 0.00 xxxx 25 ATOM 26 NE2 GLN A 3 39.133 38.666 102.650 1.00 0.00 xxxx 26 ATOM 27 N LEU A 4 43.922 35.808 100.729 1.00 0.00 xxxx 27 ATOM 28 CA LEU A 4 44.155 35.405 99.356 1.00 0.00 xxxx 28 ATOM 29 C LEU A 4 42.819 35.406 98.634 1.00 0.00 xxxx 29 ATOM 30 O LEU A 4 41.807 34.955 99.179 1.00 0.00 xxxx 30 ATOM 31 CB LEU A 4 44.758 33.999 99.317 1.00 0.00 xxxx 31 ATOM 32 CG LEU A 4 46.128 33.906 99.989 1.00 0.00 xxxx 32 ATOM 33 CD1 LEU A 4 46.603 32.466 100.045 1.00 0.00 xxxx 33 ATOM 34 CD2 LEU A 4 47.122 34.771 99.240 1.00 0.00 xxxx 34 ATOM 35 N ASN A 5 42.816 35.928 97.417 1.00 0.00 xxxx 35 ATOM 36 CA ASN A 5 41.601 36.070 96.627 1.00 0.00 xxxx 36 ATOM 37 C ASN A 5 41.719 35.224 95.378 1.00 0.00 xxxx 37 ATOM 38 O ASN A 5 42.670 35.378 94.602 1.00 0.00 xxxx 38 ATOM 39 CB ASN A 5 41.379 37.526 96.236 1.00 0.00 xxxx 39 ATOM 40 CG ASN A 5 40.748 38.312 97.342 1.00 0.00 xxxx 40 ATOM 41 OD1 ASN A 5 39.555 38.182 97.600 1.00 0.00 xxxx 41 ATOM 42 ND2 ASN A 5 41.547 39.128 98.019 1.00 0.00 xxxx 42 ATOM 43 N ILE A 6 40.751 34.341 95.183 1.00 0.00 xxxx 43 ATOM 44 CA ILE A 6 40.687 33.487 94.005 1.00 0.00 xxxx 44 ATOM 45 C ILE A 6 39.419 33.829 93.242 1.00 0.00 xxxx 45 ATOM 46 O ILE A 6 38.324 33.826 93.814 1.00 0.00 xxxx 46 ATOM 47 CB ILE A 6 40.716 31.997 94.388 1.00 0.00 xxxx 47 ATOM 48 CG1 ILE A 6 42.005 31.679 95.151 1.00 0.00 xxxx 48 ATOM 49 CG2 ILE A 6 40.600 31.126 93.145 1.00 0.00 xxxx 49 ATOM 50 CD1 ILE A 6 41.999 30.321 95.825 1.00 0.00 xxxx 50 ATOM 51 N GLY A 7 39.570 34.145 91.963 1.00 0.00 xxxx 51 ATOM 52 CA GLY A 7 38.413 34.396 91.134 1.00 0.00 xxxx 52 ATOM 53 C GLY A 7 37.924 33.090 90.543 1.00 0.00 xxxx 53 ATOM 54 O GLY A 7 38.686 32.412 89.855 1.00 0.00 xxxx 54 ATOM 55 N VAL A 8 36.679 32.708 90.822 1.00 0.00 xxxx 55 ATOM 56 CA VAL A 8 36.120 31.439 90.353 1.00 0.00 xxxx 56 ATOM 57 C VAL A 8 34.927 31.749 89.466 1.00 0.00 xxxx 57 ATOM 58 O VAL A 8 33.987 32.428 89.901 1.00 0.00 xxxx 58 ATOM 59 CB VAL A 8 35.678 30.544 91.522 1.00 0.00 xxxx 59 ATOM 60 CG1 VAL A 8 35.179 29.191 90.997 1.00 0.00 xxxx 60 ATOM 61 CG2 VAL A 8 36.802 30.361 92.528 1.00 0.00 xxxx 61 ATOM 62 N ALA A 9 34.956 31.258 88.235 1.00 0.00 xxxx 62 ATOM 63 CA ALA A 9 33.838 31.406 87.312 1.00 0.00 xxxx 63 ATOM 64 C ALA A 9 33.262 30.028 87.040 1.00 0.00 xxxx 64 ATOM 65 O ALA A 9 33.993 29.131 86.602 1.00 0.00 xxxx 65 ATOM 66 CB ALA A 9 34.284 32.061 86.002 1.00 0.00 xxxx 66 ATOM 67 N ILE A 10 31.967 29.858 87.321 1.00 0.00 xxxx 67 ATOM 68 CA ILE A 10 31.236 28.619 87.049 1.00 0.00 xxxx 68 ATOM 69 C ILE A 10 30.422 28.837 85.784 1.00 0.00 xxxx 69 ATOM 70 O ILE A 10 29.765 29.873 85.640 1.00 0.00 xxxx 70 ATOM 71 CB ILE A 10 30.325 28.257 88.238 1.00 0.00 xxxx 71 ATOM 72 CG1 ILE A 10 31.138 28.181 89.538 1.00 0.00 xxxx 72 ATOM 73 CG2 ILE A 10 29.577 26.954 87.986 1.00 0.00 xxxx 73 ATOM 74 CD1 ILE A 10 32.132 27.050 89.563 1.00 0.00 xxxx 74 ATOM 75 N TYR A 11 30.445 27.866 84.863 1.00 0.00 xxxx 75 ATOM 76 CA TYR A 11 29.862 28.130 83.545 1.00 0.00 xxxx 76 ATOM 77 C TYR A 11 28.373 28.468 83.643 1.00 0.00 xxxx 77 ATOM 78 O TYR A 11 27.889 29.339 82.916 1.00 0.00 xxxx 78 ATOM 79 CB TYR A 11 30.170 27.001 82.546 1.00 0.00 xxxx 79 ATOM 80 CG TYR A 11 29.092 25.948 82.396 1.00 0.00 xxxx 80 ATOM 81 CD1 TYR A 11 28.144 26.043 81.384 1.00 0.00 xxxx 81 ATOM 82 CD2 TYR A 11 29.034 24.856 83.261 1.00 0.00 xxxx 82 ATOM 83 CE1 TYR A 11 27.158 25.080 81.241 1.00 0.00 xxxx 83 ATOM 84 CE2 TYR A 11 28.045 23.892 83.125 1.00 0.00 xxxx 84 ATOM 85 CZ TYR A 11 27.118 24.018 82.115 1.00 0.00 xxxx 85 ATOM 86 OH TYR A 11 26.134 23.080 81.984 1.00 0.00 xxxx 86 ATOM 87 N LYS A 12 27.630 27.782 84.516 1.00 0.00 xxxx 87 ATOM 88 CA LYS A 12 26.283 28.208 84.866 1.00 0.00 xxxx 88 ATOM 89 C LYS A 12 25.909 27.598 86.210 1.00 0.00 xxxx 89 ATOM 90 O LYS A 12 26.226 26.436 86.496 1.00 0.00 xxxx 90 ATOM 91 CB LYS A 12 25.243 27.891 83.780 1.00 0.00 xxxx 91 ATOM 92 CG LYS A 12 24.862 26.446 83.644 1.00 0.00 xxxx 92 ATOM 93 CD LYS A 12 23.817 26.256 82.538 1.00 0.00 xxxx 93 ATOM 94 CE LYS A 12 23.394 24.805 82.448 1.00 0.00 xxxx 94 ATOM 95 NZ LYS A 12 22.368 24.593 81.393 1.00 0.00 xxxx 95 ATOM 96 N PHE A 13 25.249 28.403 87.036 1.00 0.00 xxxx 96 ATOM 97 CA PHE A 13 24.853 27.945 88.361 1.00 0.00 xxxx 97 ATOM 98 C PHE A 13 23.757 26.882 88.320 1.00 0.00 xxxx 98 ATOM 99 O PHE A 13 23.655 26.093 89.267 1.00 0.00 xxxx 99 ATOM 100 CB PHE A 13 24.403 29.131 89.226 1.00 0.00 xxxx 100 ATOM 101 CG PHE A 13 25.524 29.827 89.958 1.00 0.00 xxxx 101 ATOM 102 CD1 PHE A 13 26.849 29.623 89.627 1.00 0.00 xxxx 102 ATOM 103 CD2 PHE A 13 25.234 30.700 90.997 1.00 0.00 xxxx 103 ATOM 104 CE1 PHE A 13 27.871 30.277 90.315 1.00 0.00 xxxx 104 ATOM 105 CE2 PHE A 13 26.245 31.352 91.691 1.00 0.00 xxxx 105 ATOM 106 CZ PHE A 13 27.567 31.139 91.351 1.00 0.00 xxxx 106 ATOM 107 N ASP A 14 22.962 26.805 87.251 1.00 0.00 xxxx 107 ATOM 108 CA ASP A 14 21.868 25.834 87.224 1.00 0.00 xxxx 108 ATOM 109 C ASP A 14 22.293 24.430 86.781 1.00 0.00 xxxx 109 ATOM 110 O ASP A 14 21.433 23.546 86.663 1.00 0.00 xxxx 110 ATOM 111 CB ASP A 14 20.671 26.348 86.413 1.00 0.00 xxxx 111 ATOM 112 CG ASP A 14 21.055 26.809 85.025 1.00 0.00 xxxx 112 ATOM 113 OD1 ASP A 14 22.089 27.496 84.889 1.00 0.00 xxxx 113 ATOM 114 OD2 ASP A 14 20.313 26.493 84.071 1.00 0.00 xxxx 114 ATOM 115 N ASP A 15 23.582 24.188 86.573 1.00 0.00 xxxx 115 ATOM 116 CA ASP A 15 24.059 22.858 86.222 1.00 0.00 xxxx 116 ATOM 117 C ASP A 15 24.132 22.010 87.491 1.00 0.00 xxxx 117 ATOM 118 O ASP A 15 24.761 22.414 88.478 1.00 0.00 xxxx 118 ATOM 119 CB ASP A 15 25.435 22.975 85.574 1.00 0.00 xxxx 119 ATOM 120 CG ASP A 15 25.957 21.651 85.075 1.00 0.00 xxxx 120 ATOM 121 OD1 ASP A 15 25.794 21.363 83.873 1.00 0.00 xxxx 121 ATOM 122 OD2 ASP A 15 26.530 20.893 85.881 1.00 0.00 xxxx 122 ATOM 123 N THR A 16 23.478 20.843 87.476 1.00 0.00 xxxx 123 ATOM 124 CA THR A 16 23.363 20.037 88.690 1.00 0.00 xxxx 124 ATOM 125 C THR A 16 24.724 19.543 89.166 1.00 0.00 xxxx 125 ATOM 126 O THR A 16 25.055 19.655 90.355 1.00 0.00 xxxx 126 ATOM 127 CB THR A 16 22.423 18.855 88.463 1.00 0.00 xxxx 127 ATOM 128 OG1 THR A 16 21.163 19.330 87.960 1.00 0.00 xxxx 128 ATOM 129 CG2 THR A 16 22.184 18.113 89.776 1.00 0.00 xxxx 129 ATOM 130 N PHE A 17 25.529 18.990 88.255 1.00 0.00 xxxx 130 ATOM 131 CA PHE A 17 26.844 18.493 88.656 1.00 0.00 xxxx 131 ATOM 132 C PHE A 17 27.726 19.624 89.167 1.00 0.00 xxxx 132 ATOM 133 O PHE A 17 28.395 19.494 90.206 1.00 0.00 xxxx 133 ATOM 134 CB PHE A 17 27.522 17.737 87.506 1.00 0.00 xxxx 134 ATOM 135 CG PHE A 17 28.944 17.377 87.815 1.00 0.00 xxxx 135 ATOM 136 CD1 PHE A 17 29.221 16.313 88.658 1.00 0.00 xxxx 136 ATOM 137 CD2 PHE A 17 29.992 18.137 87.324 1.00 0.00 xxxx 137 ATOM 138 CE1 PHE A 17 30.527 15.998 89.000 1.00 0.00 xxxx 138 ATOM 139 CE2 PHE A 17 31.315 17.815 87.651 1.00 0.00 xxxx 139 ATOM 140 CZ PHE A 17 31.572 16.752 88.491 1.00 0.00 xxxx 140 ATOM 141 N MET A 18 27.749 20.745 88.449 1.00 0.00 xxxx 141 ATOM 142 CA MET A 18 28.609 21.840 88.859 1.00 0.00 xxxx 142 ATOM 143 C MET A 18 28.149 22.496 90.158 1.00 0.00 xxxx 143 ATOM 144 O MET A 18 28.966 23.127 90.832 1.00 0.00 xxxx 144 ATOM 145 CB MET A 18 28.780 22.851 87.723 1.00 0.00 xxxx 145 ATOM 146 CG MET A 18 29.638 22.310 86.563 1.00 0.00 xxxx 146 ATOM 147 SD MET A 18 31.269 21.698 87.068 1.00 0.00 xxxx 147 ATOM 148 CE MET A 18 31.997 23.172 87.760 1.00 0.00 xxxx 148 ATOM 149 N THR A 19 26.872 22.368 90.531 1.00 0.00 xxxx 149 ATOM 150 CA THR A 19 26.451 22.829 91.850 1.00 0.00 xxxx 150 ATOM 151 C THR A 19 27.156 22.040 92.945 1.00 0.00 xxxx 151 ATOM 152 O THR A 19 27.605 22.608 93.946 1.00 0.00 xxxx 152 ATOM 153 CB THR A 19 24.937 22.719 91.970 1.00 0.00 xxxx 153 ATOM 154 OG1 THR A 19 24.344 23.589 90.996 1.00 0.00 xxxx 154 ATOM 155 CG2 THR A 19 24.485 23.130 93.358 1.00 0.00 xxxx 155 ATOM 156 N GLY A 20 27.297 20.729 92.755 1.00 0.00 xxxx 156 ATOM 157 CA GLY A 20 28.061 19.945 93.709 1.00 0.00 xxxx 157 ATOM 158 C GLY A 20 29.516 20.366 93.780 1.00 0.00 xxxx 158 ATOM 159 O GLY A 20 30.103 20.412 94.866 1.00 0.00 xxxx 159 ATOM 160 N VAL A 21 30.118 20.682 92.628 1.00 0.00 xxxx 160 ATOM 161 CA VAL A 21 31.509 21.135 92.614 1.00 0.00 xxxx 161 ATOM 162 C VAL A 21 31.650 22.459 93.348 1.00 0.00 xxxx 162 ATOM 163 O VAL A 21 32.525 22.622 94.203 1.00 0.00 xxxx 163 ATOM 164 CB VAL A 21 32.041 21.238 91.175 1.00 0.00 xxxx 164 ATOM 165 CG1 VAL A 21 33.437 21.844 91.180 1.00 0.00 xxxx 165 ATOM 166 CG2 VAL A 21 32.058 19.874 90.497 1.00 0.00 xxxx 166 ATOM 167 N ARG A 22 30.810 23.440 93.015 1.00 0.00 xxxx 167 ATOM 168 CA ARG A 22 31.006 24.739 93.649 1.00 0.00 xxxx 168 ATOM 169 C ARG A 22 30.718 24.699 95.149 1.00 0.00 xxxx 169 ATOM 170 O ARG A 22 31.406 25.379 95.918 1.00 0.00 xxxx 170 ATOM 171 CB ARG A 22 30.269 25.848 92.897 1.00 0.00 xxxx 171 ATOM 172 CG ARG A 22 28.782 25.708 92.836 1.00 0.00 xxxx 172 ATOM 173 CD ARG A 22 28.239 26.768 91.886 1.00 0.00 xxxx 173 ATOM 174 NE ARG A 22 26.839 26.539 91.568 1.00 0.00 xxxx 174 ATOM 175 CZ ARG A 22 25.837 26.992 92.305 1.00 0.00 xxxx 175 ATOM 176 NH1 ARG A 22 26.091 27.690 93.407 1.00 0.00 xxxx 176 ATOM 177 NH2 ARG A 22 24.585 26.746 91.952 1.00 0.00 xxxx 177 ATOM 178 N ASN A 23 29.746 23.897 95.592 1.00 0.00 xxxx 178 ATOM 179 CA ASN A 23 29.515 23.756 97.027 1.00 0.00 xxxx 179 ATOM 180 C ASN A 23 30.709 23.111 97.717 1.00 0.00 xxxx 180 ATOM 181 O ASN A 23 31.083 23.507 98.825 1.00 0.00 xxxx 181 ATOM 182 CB ASN A 23 28.260 22.929 97.291 1.00 0.00 xxxx 182 ATOM 183 CG ASN A 23 26.988 23.666 96.932 1.00 0.00 xxxx 183 ATOM 184 OD1 ASN A 23 26.978 24.886 96.797 1.00 0.00 xxxx 184 ATOM 185 ND2 ASN A 23 25.905 22.922 96.777 1.00 0.00 xxxx 185 ATOM 186 N ALA A 24 31.328 22.119 97.076 1.00 0.00 xxxx 186 ATOM 187 CA ALA A 24 32.500 21.497 97.682 1.00 0.00 xxxx 187 ATOM 188 C ALA A 24 33.708 22.429 97.666 1.00 0.00 xxxx 188 ATOM 189 O ALA A 24 34.502 22.416 98.615 1.00 0.00 xxxx 189 ATOM 190 CB ALA A 24 32.809 20.168 96.998 1.00 0.00 xxxx 190 ATOM 191 N MET A 25 33.850 23.259 96.627 1.00 0.00 xxxx 191 ATOM 192 CA MET A 25 34.940 24.231 96.613 1.00 0.00 xxxx 192 ATOM 193 C MET A 25 34.787 25.222 97.753 1.00 0.00 xxxx 193 ATOM 194 O MET A 25 35.764 25.546 98.437 1.00 0.00 xxxx 194 ATOM 195 CB MET A 25 34.981 24.968 95.270 1.00 0.00 xxxx 195 ATOM 196 CG MET A 25 35.449 24.116 94.095 1.00 0.00 xxxx 196 ATOM 197 SD MET A 25 35.613 25.003 92.534 1.00 0.00 xxxx 197 ATOM 198 CE MET A 25 36.694 26.323 93.078 1.00 0.00 xxxx 198 ATOM 199 N THR A 26 33.564 25.721 97.964 1.00 0.00 xxxx 199 ATOM 200 CA THR A 26 33.301 26.646 99.061 1.00 0.00 xxxx 200 ATOM 201 C THR A 26 33.669 26.015 100.393 1.00 0.00 xxxx 201 ATOM 202 O THR A 26 34.274 26.667 101.256 1.00 0.00 xxxx 202 ATOM 203 CB THR A 26 31.825 27.039 99.033 1.00 0.00 xxxx 203 ATOM 204 OG1 THR A 26 31.547 27.723 97.806 1.00 0.00 xxxx 204 ATOM 205 CG2 THR A 26 31.469 27.953 100.202 1.00 0.00 xxxx 205 ATOM 206 N ALA A 27 33.338 24.735 100.573 1.00 0.00 xxxx 206 ATOM 207 CA ALA A 27 33.658 24.071 101.828 1.00 0.00 xxxx 207 ATOM 208 C ALA A 27 35.165 23.922 102.008 1.00 0.00 xxxx 208 ATOM 209 O ALA A 27 35.680 24.097 103.116 1.00 0.00 xxxx 209 ATOM 210 CB ALA A 27 32.957 22.717 101.889 1.00 0.00 xxxx 210 ATOM 211 N GLU A 28 35.892 23.621 100.930 1.00 0.00 xxxx 211 ATOM 212 CA GLU A 28 37.337 23.457 101.064 1.00 0.00 xxxx 212 ATOM 213 C GLU A 28 38.032 24.785 101.340 1.00 0.00 xxxx 213 ATOM 214 O GLU A 28 39.046 24.814 102.045 1.00 0.00 xxxx 214 ATOM 215 CB GLU A 28 37.917 22.797 99.812 1.00 0.00 xxxx 215 ATOM 216 CG GLU A 28 39.357 22.325 99.980 1.00 0.00 xxxx 216 ATOM 217 CD GLU A 28 39.498 21.215 101.005 1.00 0.00 xxxx 217 ATOM 218 OE1 GLU A 28 38.534 20.443 101.189 1.00 0.00 xxxx 218 ATOM 219 OE2 GLU A 28 40.576 21.116 101.631 1.00 0.00 xxxx 219 ATOM 220 N ALA A 29 37.501 25.884 100.801 1.00 0.00 xxxx 220 ATOM 221 CA ALA A 29 38.119 27.195 100.943 1.00 0.00 xxxx 221 ATOM 222 C ALA A 29 37.903 27.814 102.314 1.00 0.00 xxxx 222 ATOM 223 O ALA A 29 38.651 28.725 102.677 1.00 0.00 xxxx 223 ATOM 224 CB ALA A 29 37.566 28.156 99.889 1.00 0.00 xxxx 224 ATOM 225 N GLN A 30 36.902 27.355 103.065 1.00 0.00 xxxx 225 ATOM 226 CA GLN A 30 36.545 27.956 104.346 1.00 0.00 xxxx 226 ATOM 227 C GLN A 30 37.751 28.033 105.270 1.00 0.00 xxxx 227 ATOM 228 O GLN A 30 38.410 27.024 105.533 1.00 0.00 xxxx 228 ATOM 229 CB GLN A 30 35.435 27.124 104.995 1.00 0.00 xxxx 229 ATOM 230 CG GLN A 30 34.875 27.717 106.281 1.00 0.00 xxxx 230 ATOM 231 CD GLN A 30 33.897 26.782 106.972 1.00 0.00 xxxx 231 ATOM 232 OE1 GLN A 30 34.295 25.762 107.534 1.00 0.00 xxxx 232 ATOM 233 NE2 GLN A 30 32.610 27.120 106.922 1.00 0.00 xxxx 233 ATOM 234 N GLY A 31 38.042 29.243 105.757 1.00 0.00 xxxx 234 ATOM 235 CA GLY A 31 39.175 29.474 106.631 1.00 0.00 xxxx 235 ATOM 236 C GLY A 31 40.523 29.560 105.946 1.00 0.00 xxxx 236 ATOM 237 O GLY A 31 41.533 29.751 106.633 1.00 0.00 xxxx 237 ATOM 238 N LYS A 32 40.578 29.446 104.618 1.00 0.00 xxxx 238 ATOM 239 CA LYS A 32 41.841 29.380 103.886 1.00 0.00 xxxx 239 ATOM 240 C LYS A 32 42.007 30.507 102.883 1.00 0.00 xxxx 240 ATOM 241 O LYS A 32 43.072 31.130 102.829 1.00 0.00 xxxx 241 ATOM 242 CB LYS A 32 41.971 28.034 103.156 1.00 0.00 xxxx 242 ATOM 243 CG LYS A 32 42.024 26.831 104.078 1.00 0.00 xxxx 243 ATOM 244 CD LYS A 32 42.100 25.541 103.276 1.00 0.00 xxxx 244 ATOM 245 CE LYS A 32 41.788 24.341 104.156 1.00 0.00 xxxx 245 ATOM 246 NZ LYS A 32 41.472 23.132 103.346 1.00 0.00 xxxx 246 ATOM 247 N ALA A 33 40.990 30.782 102.079 1.00 0.00 xxxx 247 ATOM 248 CA ALA A 33 41.101 31.780 101.029 1.00 0.00 xxxx 248 ATOM 249 C ALA A 33 39.702 32.228 100.659 1.00 0.00 xxxx 249 ATOM 250 O ALA A 33 38.728 31.492 100.837 1.00 0.00 xxxx 250 ATOM 251 CB ALA A 33 41.816 31.214 99.799 1.00 0.00 xxxx 251 ATOM 252 N LYS A 34 39.615 33.438 100.121 1.00 0.00 xxxx 252 ATOM 253 CA LYS A 34 38.337 34.001 99.709 1.00 0.00 xxxx 253 ATOM 254 C LYS A 34 38.080 33.631 98.255 1.00 0.00 xxxx 254 ATOM 255 O LYS A 34 38.876 33.970 97.373 1.00 0.00 xxxx 255 ATOM 256 CB LYS A 34 38.348 35.519 99.870 1.00 0.00 xxxx 256 ATOM 257 CG LYS A 34 37.036 36.178 99.475 1.00 0.00 xxxx 257 ATOM 258 CD LYS A 34 37.045 37.663 99.792 1.00 0.00 xxxx 258 ATOM 259 CE LYS A 34 35.786 38.332 99.252 1.00 0.00 xxxx 259 ATOM 260 NZ LYS A 34 35.790 39.805 99.460 1.00 0.00 xxxx 260 ATOM 261 N LEU A 35 36.987 32.912 98.007 1.00 0.00 xxxx 261 ATOM 262 CA LEU A 35 36.547 32.647 96.645 1.00 0.00 xxxx 262 ATOM 263 C LEU A 35 35.617 33.769 96.220 1.00 0.00 xxxx 263 ATOM 264 O LEU A 35 34.622 34.052 96.898 1.00 0.00 xxxx 264 ATOM 265 CB LEU A 35 35.817 31.311 96.533 1.00 0.00 xxxx 265 ATOM 266 CG LEU A 35 36.570 30.079 97.011 1.00 0.00 xxxx 266 ATOM 267 CD1 LEU A 35 35.771 28.820 96.682 1.00 0.00 xxxx 267 ATOM 268 CD2 LEU A 35 37.962 30.024 96.405 1.00 0.00 xxxx 268 ATOM 269 N ASN A 36 35.946 34.414 95.113 1.00 0.00 xxxx 269 ATOM 270 CA ASN A 36 35.060 35.395 94.494 1.00 0.00 xxxx 270 ATOM 271 C ASN A 36 34.382 34.638 93.360 1.00 0.00 xxxx 271 ATOM 272 O ASN A 36 34.899 34.555 92.243 1.00 0.00 xxxx 272 ATOM 273 CB ASN A 36 35.870 36.593 94.027 1.00 0.00 xxxx 273 ATOM 274 CG ASN A 36 36.557 37.289 95.182 1.00 0.00 xxxx 274 ATOM 275 OD1 ASN A 36 35.957 38.126 95.846 1.00 0.00 xxxx 275 ATOM 276 ND2 ASN A 36 37.793 36.897 95.469 1.00 0.00 xxxx 276 ATOM 277 N MET A 37 33.217 34.063 93.641 1.00 0.00 xxxx 277 ATOM 278 CA MET A 37 32.609 33.085 92.743 1.00 0.00 xxxx 278 ATOM 279 C MET A 37 31.433 33.697 91.990 1.00 0.00 xxxx 279 ATOM 280 O MET A 37 30.486 34.207 92.603 1.00 0.00 xxxx 280 ATOM 281 CB MET A 37 32.180 31.831 93.499 1.00 0.00 xxxx 281 ATOM 282 CG MET A 37 31.663 30.735 92.582 1.00 0.00 xxxx 282 ATOM 283 SD MET A 37 31.040 29.361 93.555 1.00 0.00 xxxx 283 ATOM 284 CE MET A 37 32.585 28.543 93.944 1.00 0.00 xxxx 284 ATOM 285 N VAL A 38 31.493 33.622 90.662 1.00 0.00 xxxx 285 ATOM 286 CA VAL A 38 30.527 34.240 89.764 1.00 0.00 xxxx 286 ATOM 287 C VAL A 38 29.901 33.185 88.859 1.00 0.00 xxxx 287 ATOM 288 O VAL A 38 30.500 32.143 88.569 1.00 0.00 xxxx 288 ATOM 289 CB VAL A 38 31.133 35.399 88.929 1.00 0.00 xxxx 289 ATOM 290 CG1 VAL A 38 31.703 36.485 89.833 1.00 0.00 xxxx 290 ATOM 291 CG2 VAL A 38 32.187 34.886 87.965 1.00 0.00 xxxx 291 ATOM 292 N ASP A 39 28.679 33.478 88.428 1.00 0.00 xxxx 292 ATOM 293 CA ASP A 39 27.868 32.649 87.543 1.00 0.00 xxxx 293 ATOM 294 C ASP A 39 27.994 33.221 86.135 1.00 0.00 xxxx 294 ATOM 295 O ASP A 39 27.584 34.359 85.879 1.00 0.00 xxxx 295 ATOM 296 CB ASP A 39 26.413 32.740 88.030 1.00 0.00 xxxx 296 ATOM 297 CG ASP A 39 25.435 31.916 87.197 1.00 0.00 xxxx 297 ATOM 298 OD1 ASP A 39 25.864 31.210 86.273 1.00 0.00 xxxx 298 ATOM 299 OD2 ASP A 39 24.217 31.984 87.482 1.00 0.00 xxxx 299 ATOM 300 N SER A 40 28.582 32.448 85.224 1.00 0.00 xxxx 300 ATOM 301 CA SER A 40 28.718 32.933 83.852 1.00 0.00 xxxx 301 ATOM 302 C SER A 40 27.437 32.805 83.040 1.00 0.00 xxxx 302 ATOM 303 O SER A 40 27.412 33.251 81.888 1.00 0.00 xxxx 303 ATOM 304 CB SER A 40 29.876 32.232 83.136 1.00 0.00 xxxx 304 ATOM 305 OG SER A 40 31.102 32.449 83.831 1.00 0.00 xxxx 305 ATOM 306 N GLN A 41 26.383 32.212 83.608 1.00 0.00 xxxx 306 ATOM 307 CA GLN A 41 25.049 32.190 83.005 1.00 0.00 xxxx 307 ATOM 308 C GLN A 41 25.053 31.588 81.602 1.00 0.00 xxxx 308 ATOM 309 O GLN A 41 24.299 32.010 80.720 1.00 0.00 xxxx 309 ATOM 310 CB GLN A 41 24.394 33.572 83.017 1.00 0.00 xxxx 310 ATOM 311 CG GLN A 41 24.215 34.163 84.415 1.00 0.00 xxxx 311 ATOM 312 CD GLN A 41 23.401 35.430 84.386 1.00 0.00 xxxx 312 ATOM 313 OE1 GLN A 41 23.931 36.521 84.568 1.00 0.00 xxxx 313 ATOM 314 NE2 GLN A 41 22.103 35.294 84.144 1.00 0.00 xxxx 314 ATOM 315 N ASN A 42 25.921 30.598 81.388 1.00 0.00 xxxx 315 ATOM 316 CA ASN A 42 25.990 29.866 80.122 1.00 0.00 xxxx 316 ATOM 317 C ASN A 42 26.345 30.772 78.942 1.00 0.00 xxxx 317 ATOM 318 O ASN A 42 25.944 30.504 77.809 1.00 0.00 xxxx 318 ATOM 319 CB ASN A 42 24.694 29.085 79.850 1.00 0.00 xxxx 319 ATOM 320 CG ASN A 42 24.907 27.888 78.954 1.00 0.00 xxxx 320 ATOM 321 OD1 ASN A 42 23.973 27.408 78.298 1.00 0.00 xxxx 321 ATOM 322 ND2 ASN A 42 26.124 27.401 78.908 1.00 0.00 xxxx 322 ATOM 323 N SER A 43 27.103 31.840 79.204 1.00 0.00 xxxx 323 ATOM 324 CA SER A 43 27.490 32.810 78.185 1.00 0.00 xxxx 324 ATOM 325 C SER A 43 28.996 33.028 78.247 1.00 0.00 xxxx 325 ATOM 326 O SER A 43 29.512 33.541 79.245 1.00 0.00 xxxx 326 ATOM 327 CB SER A 43 26.766 34.134 78.438 1.00 0.00 xxxx 327 ATOM 328 OG SER A 43 27.295 35.177 77.627 1.00 0.00 xxxx 328 ATOM 329 N GLN A 44 29.707 32.653 77.183 1.00 0.00 xxxx 329 ATOM 330 CA GLN A 44 31.145 32.903 77.183 1.00 0.00 xxxx 330 ATOM 331 C GLN A 44 31.464 34.397 77.155 1.00 0.00 xxxx 331 ATOM 332 O GLN A 44 32.416 34.810 77.829 1.00 0.00 xxxx 332 ATOM 333 CB GLN A 44 31.877 32.158 76.060 1.00 0.00 xxxx 333 ATOM 334 CG GLN A 44 33.404 32.203 76.217 1.00 0.00 xxxx 334 ATOM 335 CD GLN A 44 33.891 31.519 77.490 1.00 0.00 xxxx 335 ATOM 336 OE1 GLN A 44 33.482 30.407 77.804 1.00 0.00 xxxx 336 ATOM 337 NE2 GLN A 44 34.769 32.193 78.233 1.00 0.00 xxxx 337 ATOM 338 N PRO A 45 30.726 35.240 76.409 1.00 0.00 xxxx 338 ATOM 339 CA PRO A 45 30.953 36.693 76.549 1.00 0.00 xxxx 339 ATOM 340 C PRO A 45 30.815 37.191 77.980 1.00 0.00 xxxx 340 ATOM 341 O PRO A 45 31.629 38.014 78.421 1.00 0.00 xxxx 341 ATOM 342 CB PRO A 45 29.924 37.307 75.589 1.00 0.00 xxxx 342 ATOM 343 CG PRO A 45 29.751 36.260 74.530 1.00 0.00 xxxx 343 ATOM 344 CD PRO A 45 29.797 34.957 75.292 1.00 0.00 xxxx 344 ATOM 345 N THR A 46 29.825 36.701 78.730 1.00 0.00 xxxx 345 ATOM 346 CA THR A 46 29.725 37.065 80.142 1.00 0.00 xxxx 346 ATOM 347 C THR A 46 30.965 36.622 80.903 1.00 0.00 xxxx 347 ATOM 348 O THR A 46 31.536 37.383 81.693 1.00 0.00 xxxx 348 ATOM 349 CB THR A 46 28.468 36.445 80.753 1.00 0.00 xxxx 349 ATOM 350 OG1 THR A 46 27.309 36.962 80.093 1.00 0.00 xxxx 350 ATOM 351 CG2 THR A 46 28.374 36.765 82.240 1.00 0.00 xxxx 351 ATOM 352 N GLN A 47 31.397 35.377 80.687 1.00 0.00 xxxx 352 ATOM 353 CA GLN A 47 32.586 34.892 81.372 1.00 0.00 xxxx 353 ATOM 354 C GLN A 47 33.819 35.708 81.003 1.00 0.00 xxxx 354 ATOM 355 O GLN A 47 34.664 35.984 81.863 1.00 0.00 xxxx 355 ATOM 356 CB GLN A 47 32.806 33.415 81.067 1.00 0.00 xxxx 356 ATOM 357 CG GLN A 47 33.924 32.840 81.894 1.00 0.00 xxxx 357 ATOM 358 CD GLN A 47 34.000 31.341 81.767 1.00 0.00 xxxx 358 ATOM 359 OE1 GLN A 47 34.729 30.823 80.926 1.00 0.00 xxxx 359 ATOM 360 NE2 GLN A 47 33.239 30.638 82.593 1.00 0.00 xxxx 360 ATOM 361 N ASN A 48 33.944 36.101 79.733 1.00 0.00 xxxx 361 ATOM 362 CA ASN A 48 35.106 36.886 79.329 1.00 0.00 xxxx 362 ATOM 363 C ASN A 48 35.147 38.210 80.081 1.00 0.00 xxxx 363 ATOM 364 O ASN A 48 36.215 38.640 80.526 1.00 0.00 xxxx 364 ATOM 365 CB ASN A 48 35.093 37.119 77.818 1.00 0.00 xxxx 365 ATOM 366 CG ASN A 48 35.338 35.844 77.022 1.00 0.00 xxxx 366 ATOM 367 OD1 ASN A 48 35.813 34.837 77.560 1.00 0.00 xxxx 367 ATOM 368 ND2 ASN A 48 35.005 35.879 75.742 1.00 0.00 xxxx 368 ATOM 369 N ASP A 49 33.984 38.847 80.264 1.00 0.00 xxxx 369 ATOM 370 CA ASP A 49 33.916 40.074 81.054 1.00 0.00 xxxx 370 ATOM 371 C ASP A 49 34.280 39.820 82.512 1.00 0.00 xxxx 371 ATOM 372 O ASP A 49 34.934 40.660 83.147 1.00 0.00 xxxx 372 ATOM 373 CB ASP A 49 32.508 40.675 80.986 1.00 0.00 xxxx 373 ATOM 374 CG ASP A 49 32.154 41.215 79.609 1.00 0.00 xxxx 374 ATOM 375 OD1 ASP A 49 33.076 41.514 78.817 1.00 0.00 xxxx 375 ATOM 376 OD2 ASP A 49 30.936 41.359 79.327 1.00 0.00 xxxx 376 ATOM 377 N GLN A 50 33.840 38.683 83.065 1.00 0.00 xxxx 377 ATOM 378 CA GLN A 50 34.152 38.357 84.456 1.00 0.00 xxxx 378 ATOM 379 C GLN A 50 35.644 38.123 84.643 1.00 0.00 xxxx 379 ATOM 380 O GLN A 50 36.229 38.561 85.640 1.00 0.00 xxxx 380 ATOM 381 CB GLN A 50 33.346 37.126 84.890 1.00 0.00 xxxx 381 ATOM 382 CG GLN A 50 31.866 37.420 85.041 1.00 0.00 xxxx 382 ATOM 383 CD GLN A 50 30.984 36.172 85.027 1.00 0.00 xxxx 383 ATOM 384 OE1 GLN A 50 31.348 35.136 84.463 1.00 0.00 xxxx 384 ATOM 385 NE2 GLN A 50 29.819 36.278 85.644 1.00 0.00 xxxx 385 ATOM 386 N VAL A 51 36.277 37.439 83.691 1.00 0.00 xxxx 386 ATOM 387 CA VAL A 51 37.723 37.252 83.744 1.00 0.00 xxxx 387 ATOM 388 C VAL A 51 38.437 38.594 83.676 1.00 0.00 xxxx 388 ATOM 389 O VAL A 51 39.393 38.843 84.424 1.00 0.00 xxxx 389 ATOM 390 CB VAL A 51 38.168 36.313 82.613 1.00 0.00 xxxx 390 ATOM 391 CG1 VAL A 51 39.692 36.311 82.501 1.00 0.00 xxxx 391 ATOM 392 CG2 VAL A 51 37.640 34.914 82.858 1.00 0.00 xxxx 392 ATOM 393 N ASP A 52 37.987 39.480 82.783 1.00 0.00 xxxx 393 ATOM 394 CA ASP A 52 38.587 40.807 82.716 1.00 0.00 xxxx 394 ATOM 395 C ASP A 52 38.515 41.507 84.069 1.00 0.00 xxxx 395 ATOM 396 O ASP A 52 39.484 42.144 84.500 1.00 0.00 xxxx 396 ATOM 397 CB ASP A 52 37.899 41.657 81.645 1.00 0.00 xxxx 397 ATOM 398 CG ASP A 52 38.259 41.239 80.228 1.00 0.00 xxxx 398 ATOM 399 OD1 ASP A 52 39.185 40.416 80.046 1.00 0.00 xxxx 399 ATOM 400 OD2 ASP A 52 37.614 41.754 79.288 1.00 0.00 xxxx 400 ATOM 401 N LEU A 53 37.374 41.403 84.754 1.00 0.00 xxxx 401 ATOM 402 CA LEU A 53 37.227 42.087 86.038 1.00 0.00 xxxx 402 ATOM 403 C LEU A 53 38.088 41.440 87.121 1.00 0.00 xxxx 403 ATOM 404 O LEU A 53 38.674 42.141 87.954 1.00 0.00 xxxx 404 ATOM 405 CB LEU A 53 35.758 42.117 86.454 1.00 0.00 xxxx 405 ATOM 406 CG LEU A 53 35.448 42.973 87.687 1.00 0.00 xxxx 406 ATOM 407 CD1 LEU A 53 35.863 44.424 87.464 1.00 0.00 xxxx 407 ATOM 408 CD2 LEU A 53 33.967 42.886 88.029 1.00 0.00 xxxx 408 ATOM 409 N PHE A 54 38.176 40.109 87.135 1.00 0.00 xxxx 409 ATOM 410 CA PHE A 54 39.078 39.445 88.071 1.00 0.00 xxxx 410 ATOM 411 C PHE A 54 40.501 39.957 87.905 1.00 0.00 xxxx 411 ATOM 412 O PHE A 54 41.227 40.139 88.889 1.00 0.00 xxxx 412 ATOM 413 CB PHE A 54 39.098 37.940 87.795 1.00 0.00 xxxx 413 ATOM 414 CG PHE A 54 37.895 37.183 88.296 1.00 0.00 xxxx 414 ATOM 415 CD1 PHE A 54 37.168 37.619 89.387 1.00 0.00 xxxx 415 ATOM 416 CD2 PHE A 54 37.503 36.017 87.661 1.00 0.00 xxxx 416 ATOM 417 CE1 PHE A 54 36.072 36.896 89.840 1.00 0.00 xxxx 417 ATOM 418 CE2 PHE A 54 36.407 35.290 88.111 1.00 0.00 xxxx 418 ATOM 419 CZ PHE A 54 35.692 35.739 89.193 1.00 0.00 xxxx 419 ATOM 420 N ILE A 55 40.929 40.159 86.657 1.00 0.00 xxxx 420 ATOM 421 CA ILE A 55 42.280 40.634 86.395 1.00 0.00 xxxx 421 ATOM 422 C ILE A 55 42.449 42.073 86.874 1.00 0.00 xxxx 422 ATOM 423 O ILE A 55 43.450 42.413 87.519 1.00 0.00 xxxx 423 ATOM 424 CB ILE A 55 42.612 40.457 84.901 1.00 0.00 xxxx 424 ATOM 425 CG1 ILE A 55 42.783 38.969 84.590 1.00 0.00 xxxx 425 ATOM 426 CG2 ILE A 55 43.853 41.263 84.512 1.00 0.00 xxxx 426 ATOM 427 CD1 ILE A 55 42.900 38.654 83.114 1.00 0.00 xxxx 427 ATOM 428 N THR A 56 41.470 42.941 86.588 1.00 0.00 xxxx 428 ATOM 429 CA THR A 56 41.569 44.323 87.048 1.00 0.00 xxxx 429 ATOM 430 C THR A 56 41.538 44.409 88.569 1.00 0.00 xxxx 430 ATOM 431 O THR A 56 42.149 45.310 89.155 1.00 0.00 xxxx 431 ATOM 432 CB THR A 56 40.458 45.172 86.432 1.00 0.00 xxxx 432 ATOM 433 OG1 THR A 56 39.187 44.752 86.937 1.00 0.00 xxxx 433 ATOM 434 CG2 THR A 56 40.467 45.040 84.930 1.00 0.00 xxxx 434 ATOM 435 N LYS A 57 40.841 43.486 89.223 1.00 0.00 xxxx 435 ATOM 436 CA LYS A 57 40.787 43.451 90.680 1.00 0.00 xxxx 436 ATOM 437 C LYS A 57 41.975 42.728 91.294 1.00 0.00 xxxx 437 ATOM 438 O LYS A 57 42.015 42.567 92.519 1.00 0.00 xxxx 438 ATOM 439 CB LYS A 57 39.490 42.779 91.139 1.00 0.00 xxxx 439 ATOM 440 CG LYS A 57 38.236 43.606 90.893 1.00 0.00 xxxx 440 ATOM 441 CD LYS A 57 36.997 42.845 91.342 1.00 0.00 xxxx 441 ATOM 442 CE LYS A 57 35.754 43.721 91.300 1.00 0.00 xxxx 442 ATOM 443 NZ LYS A 57 34.543 42.975 91.742 1.00 0.00 xxxx 443 ATOM 444 N LYS A 58 42.920 42.268 90.474 1.00 0.00 xxxx 444 ATOM 445 CA LYS A 58 44.163 41.654 90.948 1.00 0.00 xxxx 445 ATOM 446 C LYS A 58 43.915 40.432 91.838 1.00 0.00 xxxx 446 ATOM 447 O LYS A 58 44.473 40.308 92.930 1.00 0.00 xxxx 447 ATOM 448 CB LYS A 58 45.084 42.677 91.621 1.00 0.00 xxxx 448 ATOM 449 CG LYS A 58 45.491 43.832 90.708 1.00 0.00 xxxx 449 ATOM 450 CD LYS A 58 46.466 44.767 91.415 1.00 0.00 xxxx 450 ATOM 451 CE LYS A 58 46.876 45.934 90.528 1.00 0.00 xxxx 451 ATOM 452 NZ LYS A 58 47.689 45.497 89.360 1.00 0.00 xxxx 452 ATOM 453 N MET A 59 43.076 39.515 91.355 1.00 0.00 xxxx 453 ATOM 454 CA MET A 59 42.977 38.209 91.994 1.00 0.00 xxxx 454 ATOM 455 C MET A 59 44.359 37.567 92.043 1.00 0.00 xxxx 455 ATOM 456 O MET A 59 45.208 37.809 91.177 1.00 0.00 xxxx 456 ATOM 457 CB MET A 59 42.041 37.296 91.195 1.00 0.00 xxxx 457 ATOM 458 CG MET A 59 40.570 37.704 91.162 1.00 0.00 xxxx 458 ATOM 459 SD MET A 59 39.731 37.646 92.761 1.00 0.00 xxxx 459 ATOM 460 CE MET A 59 39.788 39.371 93.232 1.00 0.00 xxxx 460 ATOM 461 N ASN A 60 44.589 36.749 93.080 1.00 0.00 xxxx 461 ATOM 462 CA ASN A 60 45.864 36.048 93.213 1.00 0.00 xxxx 462 ATOM 463 C ASN A 60 45.940 34.809 92.329 1.00 0.00 xxxx 463 ATOM 464 O ASN A 60 47.045 34.367 91.978 1.00 0.00 xxxx 464 ATOM 465 CB ASN A 60 46.117 35.663 94.677 1.00 0.00 xxxx 465 ATOM 466 CG ASN A 60 46.186 36.866 95.592 1.00 0.00 xxxx 466 ATOM 467 OD1 ASN A 60 45.232 37.173 96.299 1.00 0.00 xxxx 467 ATOM 468 ND2 ASN A 60 47.323 37.552 95.584 1.00 0.00 xxxx 468 ATOM 469 N ALA A 61 44.793 34.248 91.968 1.00 0.00 xxxx 469 ATOM 470 CA ALA A 61 44.730 33.123 91.049 1.00 0.00 xxxx 470 ATOM 471 C ALA A 61 43.314 33.070 90.501 1.00 0.00 xxxx 471 ATOM 472 O ALA A 61 42.387 33.651 91.072 1.00 0.00 xxxx 472 ATOM 473 CB ALA A 61 45.102 31.798 91.738 1.00 0.00 xxxx 473 ATOM 474 N LEU A 62 43.161 32.376 89.375 1.00 0.00 xxxx 474 ATOM 475 CA LEU A 62 41.862 32.166 88.747 1.00 0.00 xxxx 475 ATOM 476 C LEU A 62 41.563 30.678 88.674 1.00 0.00 xxxx 476 ATOM 477 O LEU A 62 42.460 29.874 88.422 1.00 0.00 xxxx 477 ATOM 478 CB LEU A 62 41.854 32.700 87.318 1.00 0.00 xxxx 478 ATOM 479 CG LEU A 62 42.259 34.157 87.163 1.00 0.00 xxxx 479 ATOM 480 CD1 LEU A 62 42.234 34.565 85.685 1.00 0.00 xxxx 480 ATOM 481 CD2 LEU A 62 41.333 35.015 87.996 1.00 0.00 xxxx 481 ATOM 482 N ALA A 63 40.294 30.331 88.884 1.00 0.00 xxxx 482 ATOM 483 CA ALA A 63 39.776 28.979 88.669 1.00 0.00 xxxx 483 ATOM 484 C ALA A 63 38.579 29.137 87.743 1.00 0.00 xxxx 484 ATOM 485 O ALA A 63 37.558 29.721 88.136 1.00 0.00 xxxx 485 ATOM 486 CB ALA A 63 39.374 28.307 89.990 1.00 0.00 xxxx 486 ATOM 487 N ILE A 64 38.705 28.644 86.509 1.00 0.00 xxxx 487 ATOM 488 CA ILE A 64 37.737 28.928 85.451 1.00 0.00 xxxx 488 ATOM 489 C ILE A 64 37.144 27.627 84.929 1.00 0.00 xxxx 489 ATOM 490 O ILE A 64 37.870 26.740 84.477 1.00 0.00 xxxx 490 ATOM 491 CB ILE A 64 38.361 29.719 84.285 1.00 0.00 xxxx 491 ATOM 492 CG1 ILE A 64 39.018 31.018 84.786 1.00 0.00 xxxx 492 ATOM 493 CD1 ILE A 64 38.075 31.990 85.470 1.00 0.00 xxxx 493 ATOM 494 CG2 ILE A 64 37.297 29.986 83.205 1.00 0.00 xxxx 494 ATOM 495 N ASN A 65 35.821 27.545 84.951 1.00 0.00 xxxx 495 ATOM 496 CA ASN A 65 35.047 26.466 84.354 1.00 0.00 xxxx 496 ATOM 497 C ASN A 65 34.469 27.053 83.070 1.00 0.00 xxxx 497 ATOM 498 O ASN A 65 33.449 27.756 83.123 1.00 0.00 xxxx 498 ATOM 499 CB ASN A 65 33.940 26.087 85.351 1.00 0.00 xxxx 499 ATOM 500 CG ASN A 65 32.918 25.098 84.818 1.00 0.00 xxxx 500 ATOM 501 OD1 ASN A 65 31.715 25.263 85.062 1.00 0.00 xxxx 501 ATOM 502 ND2 ASN A 65 33.364 24.068 84.105 1.00 0.00 xxxx 502 ATOM 503 N PRO A 66 35.101 26.838 81.906 1.00 0.00 xxxx 503 ATOM 504 CA PRO A 66 34.677 27.548 80.684 1.00 0.00 xxxx 504 ATOM 505 C PRO A 66 33.239 27.261 80.289 1.00 0.00 xxxx 505 ATOM 506 O PRO A 66 32.722 26.159 80.478 1.00 0.00 xxxx 506 ATOM 507 CB PRO A 66 35.636 27.022 79.610 1.00 0.00 xxxx 507 ATOM 508 CG PRO A 66 36.833 26.497 80.362 1.00 0.00 xxxx 508 ATOM 509 CD PRO A 66 36.293 25.996 81.686 1.00 0.00 xxxx 509 ATOM 510 N VAL A 67 32.607 28.264 79.673 1.00 0.00 xxxx 510 ATOM 511 CA VAL A 67 31.380 27.994 78.935 1.00 0.00 xxxx 511 ATOM 512 C VAL A 67 31.706 27.288 77.625 1.00 0.00 xxxx 512 ATOM 513 O VAL A 67 31.181 26.207 77.331 1.00 0.00 xxxx 513 ATOM 514 CB VAL A 67 30.587 29.294 78.713 1.00 0.00 xxxx 514 ATOM 515 CG1 VAL A 67 29.312 29.005 77.929 1.00 0.00 xxxx 515 ATOM 516 CG2 VAL A 67 30.270 29.937 80.054 1.00 0.00 xxxx 516 ATOM 517 N ASP A 68 32.586 27.896 76.825 1.00 0.00 xxxx 517 ATOM 518 CA ASP A 68 33.089 27.344 75.570 1.00 0.00 xxxx 518 ATOM 519 C ASP A 68 34.566 27.052 75.820 1.00 0.00 xxxx 519 ATOM 520 O ASP A 68 35.363 27.978 75.992 1.00 0.00 xxxx 520 ATOM 521 CB ASP A 68 32.902 28.403 74.483 1.00 0.00 xxxx 521 ATOM 522 CG ASP A 68 33.509 28.022 73.150 1.00 0.00 xxxx 522 ATOM 523 OD1 ASP A 68 34.190 26.984 73.041 1.00 0.00 xxxx 523 ATOM 524 OD2 ASP A 68 33.299 28.793 72.184 1.00 0.00 xxxx 524 ATOM 525 N ARG A 69 34.938 25.771 75.870 1.00 0.00 xxxx 525 ATOM 526 CA ARG A 69 36.314 25.449 76.240 1.00 0.00 xxxx 526 ATOM 527 C ARG A 69 37.342 25.935 75.220 1.00 0.00 xxxx 527 ATOM 528 O ARG A 69 38.520 26.068 75.573 1.00 0.00 xxxx 528 ATOM 529 CB ARG A 69 36.478 23.954 76.527 1.00 0.00 xxxx 529 ATOM 530 CG ARG A 69 36.394 23.077 75.307 1.00 0.00 xxxx 530 ATOM 531 CD ARG A 69 36.008 21.656 75.723 1.00 0.00 xxxx 531 ATOM 532 NE ARG A 69 35.941 20.732 74.600 1.00 0.00 xxxx 532 ATOM 533 CZ ARG A 69 36.959 19.992 74.168 1.00 0.00 xxxx 533 ATOM 534 NH1 ARG A 69 38.142 20.069 74.758 1.00 0.00 xxxx 534 ATOM 535 NH2 ARG A 69 36.789 19.184 73.138 1.00 0.00 xxxx 535 ATOM 536 N THR A 70 36.934 26.219 73.984 1.00 0.00 xxxx 536 ATOM 537 CA THR A 70 37.874 26.788 73.025 1.00 0.00 xxxx 537 ATOM 538 C THR A 70 38.253 28.221 73.383 1.00 0.00 xxxx 538 ATOM 539 O THR A 70 39.257 28.731 72.874 1.00 0.00 xxxx 539 ATOM 540 CB THR A 70 37.344 26.680 71.590 1.00 0.00 xxxx 540 ATOM 541 OG1 THR A 70 36.207 27.530 71.423 1.00 0.00 xxxx 541 ATOM 542 CG2 THR A 70 36.956 25.244 71.267 1.00 0.00 xxxx 542 ATOM 543 N ALA A 71 37.482 28.876 74.253 1.00 0.00 xxxx 543 ATOM 544 CA ALA A 71 37.821 30.216 74.719 1.00 0.00 xxxx 544 ATOM 545 C ALA A 71 38.947 30.224 75.737 1.00 0.00 xxxx 545 ATOM 546 O ALA A 71 39.421 31.308 76.104 1.00 0.00 xxxx 546 ATOM 547 CB ALA A 71 36.596 30.899 75.331 1.00 0.00 xxxx 547 ATOM 548 N ALA A 72 39.407 29.056 76.180 1.00 0.00 xxxx 548 ATOM 549 CA ALA A 72 40.478 29.019 77.168 1.00 0.00 xxxx 549 ATOM 550 C ALA A 72 41.765 29.642 76.638 1.00 0.00 xxxx 550 ATOM 551 O ALA A 72 42.545 30.201 77.417 1.00 0.00 xxxx 551 ATOM 552 CB ALA A 72 40.710 27.581 77.640 1.00 0.00 xxxx 552 ATOM 553 N GLY A 73 41.988 29.591 75.324 1.00 0.00 xxxx 553 ATOM 554 CA GLY A 73 43.196 30.180 74.765 1.00 0.00 xxxx 554 ATOM 555 C GLY A 73 43.308 31.668 75.049 1.00 0.00 xxxx 555 ATOM 556 O GLY A 73 44.358 32.156 75.469 1.00 0.00 xxxx 556 ATOM 557 N THR A 74 42.218 32.404 74.826 1.00 0.00 xxxx 557 ATOM 558 CA THR A 74 42.237 33.842 75.074 1.00 0.00 xxxx 558 ATOM 559 C THR A 74 42.330 34.142 76.565 1.00 0.00 xxxx 559 ATOM 560 O THR A 74 43.006 35.094 76.973 1.00 0.00 xxxx 560 ATOM 561 CB THR A 74 40.990 34.484 74.469 1.00 0.00 xxxx 561 ATOM 562 OG1 THR A 74 40.899 34.126 73.085 1.00 0.00 xxxx 562 ATOM 563 CG2 THR A 74 41.061 35.997 74.587 1.00 0.00 xxxx 563 ATOM 564 N ILE A 75 41.662 33.340 77.393 1.00 0.00 xxxx 564 ATOM 565 CA ILE A 75 41.765 33.525 78.838 1.00 0.00 xxxx 565 ATOM 566 C ILE A 75 43.202 33.322 79.304 1.00 0.00 xxxx 566 ATOM 567 O ILE A 75 43.710 34.083 80.138 1.00 0.00 xxxx 567 ATOM 568 CB ILE A 75 40.771 32.605 79.565 1.00 0.00 xxxx 568 ATOM 569 CG1 ILE A 75 39.344 33.021 79.219 1.00 0.00 xxxx 569 ATOM 570 CG2 ILE A 75 40.994 32.655 81.070 1.00 0.00 xxxx 570 ATOM 571 CD1 ILE A 75 38.305 32.030 79.674 1.00 0.00 xxxx 571 ATOM 572 N ILE A 76 43.887 32.309 78.757 1.00 0.00 xxxx 572 ATOM 573 CA ILE A 76 45.294 32.094 79.085 1.00 0.00 xxxx 573 ATOM 574 C ILE A 76 46.139 33.290 78.665 1.00 0.00 xxxx 574 ATOM 575 O ILE A 76 47.021 33.729 79.412 1.00 0.00 xxxx 575 ATOM 576 CB ILE A 76 45.804 30.775 78.476 1.00 0.00 xxxx 576 ATOM 577 CG1 ILE A 76 45.122 29.589 79.156 1.00 0.00 xxxx 577 ATOM 578 CG2 ILE A 76 47.316 30.664 78.638 1.00 0.00 xxxx 578 ATOM 579 CD1 ILE A 76 45.268 28.282 78.392 1.00 0.00 xxxx 579 ATOM 580 N ASP A 77 45.887 33.840 77.467 1.00 0.00 xxxx 580 ATOM 581 CA ASP A 77 46.636 35.016 77.025 1.00 0.00 xxxx 581 ATOM 582 C ASP A 77 46.484 36.159 78.020 1.00 0.00 xxxx 582 ATOM 583 O ASP A 77 47.464 36.818 78.387 1.00 0.00 xxxx 583 ATOM 584 CB ASP A 77 46.158 35.467 75.644 1.00 0.00 xxxx 584 ATOM 585 CG ASP A 77 46.590 34.533 74.533 1.00 0.00 xxxx 585 ATOM 586 OD1 ASP A 77 47.614 33.841 74.696 1.00 0.00 xxxx 586 ATOM 587 OD2 ASP A 77 45.904 34.500 73.489 1.00 0.00 xxxx 587 ATOM 588 N LYS A 78 45.253 36.401 78.471 1.00 0.00 xxxx 588 ATOM 589 CA LYS A 78 45.010 37.504 79.394 1.00 0.00 xxxx 589 ATOM 590 C LYS A 78 45.652 37.237 80.747 1.00 0.00 xxxx 590 ATOM 591 O LYS A 78 46.258 38.138 81.339 1.00 0.00 xxxx 591 ATOM 592 CB LYS A 78 43.507 37.715 79.564 1.00 0.00 xxxx 592 ATOM 593 CG LYS A 78 42.806 38.240 78.327 1.00 0.00 xxxx 593 ATOM 594 CD LYS A 78 41.302 38.175 78.521 1.00 0.00 xxxx 594 ATOM 595 CE LYS A 78 40.571 38.956 77.442 1.00 0.00 xxxx 595 ATOM 596 NZ LYS A 78 39.097 38.909 77.649 1.00 0.00 xxxx 596 ATOM 597 N ALA A 79 45.525 36.008 81.251 1.00 0.00 xxxx 597 ATOM 598 CA ALA A 79 46.115 35.671 82.541 1.00 0.00 xxxx 598 ATOM 599 C ALA A 79 47.635 35.750 82.490 1.00 0.00 xxxx 599 ATOM 600 O ALA A 79 48.268 36.274 83.414 1.00 0.00 xxxx 600 ATOM 601 CB ALA A 79 45.666 34.273 82.964 1.00 0.00 xxxx 601 ATOM 602 N LYS A 80 48.238 35.242 81.412 1.00 0.00 xxxx 602 ATOM 603 CA LYS A 80 49.691 35.320 81.266 1.00 0.00 xxxx 603 ATOM 604 C LYS A 80 50.169 36.768 81.250 1.00 0.00 xxxx 604 ATOM 605 O LYS A 80 51.180 37.105 81.878 1.00 0.00 xxxx 605 ATOM 606 CB LYS A 80 50.113 34.607 79.981 1.00 0.00 xxxx 606 ATOM 607 CG LYS A 80 51.616 34.566 79.750 1.00 0.00 xxxx 607 ATOM 608 CD LYS A 80 51.944 33.783 78.485 1.00 0.00 xxxx 608 ATOM 609 CE LYS A 80 53.444 33.672 78.273 1.00 0.00 xxxx 609 ATOM 610 NZ LYS A 80 53.760 32.800 77.108 1.00 0.00 xxxx 610 ATOM 611 N GLN A 81 49.453 37.640 80.537 1.00 0.00 xxxx 611 ATOM 612 CA GLN A 81 49.845 39.044 80.476 1.00 0.00 xxxx 612 ATOM 613 C GLN A 81 49.766 39.701 81.849 1.00 0.00 xxxx 613 ATOM 614 O GLN A 81 50.602 40.547 82.187 1.00 0.00 xxxx 614 ATOM 615 CB GLN A 81 48.974 39.782 79.461 1.00 0.00 xxxx 615 ATOM 616 CG GLN A 81 49.389 41.224 79.220 1.00 0.00 xxxx 616 ATOM 617 CD GLN A 81 50.816 41.343 78.709 1.00 0.00 xxxx 617 ATOM 618 OE1 GLN A 81 51.242 40.586 77.835 1.00 0.00 xxxx 618 ATOM 619 NE2 GLN A 81 51.566 42.293 79.262 1.00 0.00 xxxx 619 ATOM 620 N ALA A 82 48.780 39.312 82.660 1.00 0.00 xxxx 620 ATOM 621 CA ALA A 82 48.623 39.844 84.008 1.00 0.00 xxxx 621 ATOM 622 C ALA A 82 49.461 39.096 85.034 1.00 0.00 xxxx 622 ATOM 623 O ALA A 82 49.497 39.505 86.201 1.00 0.00 xxxx 623 ATOM 624 CB ALA A 82 47.153 39.754 84.433 1.00 0.00 xxxx 624 ATOM 625 N ASN A 83 50.124 38.015 84.625 1.00 0.00 xxxx 625 ATOM 626 CA ASN A 83 50.869 37.141 85.534 1.00 0.00 xxxx 626 ATOM 627 C ASN A 83 49.992 36.622 86.673 1.00 0.00 xxxx 627 ATOM 628 O ASN A 83 50.401 36.599 87.834 1.00 0.00 xxxx 628 ATOM 629 CB ASN A 83 52.149 37.799 86.058 1.00 0.00 xxxx 629 ATOM 630 CG ASN A 83 53.128 36.794 86.629 1.00 0.00 xxxx 630 ATOM 631 OD1 ASN A 83 53.159 35.632 86.215 1.00 0.00 xxxx 631 ATOM 632 ND2 ASN A 83 53.924 37.229 87.597 1.00 0.00 xxxx 632 ATOM 633 N ILE A 84 48.776 36.201 86.341 1.00 0.00 xxxx 633 ATOM 634 CA ILE A 84 47.852 35.601 87.298 1.00 0.00 xxxx 634 ATOM 635 C ILE A 84 47.658 34.144 86.894 1.00 0.00 xxxx 635 ATOM 636 O ILE A 84 47.107 33.871 85.815 1.00 0.00 xxxx 636 ATOM 637 CB ILE A 84 46.518 36.361 87.359 1.00 0.00 xxxx 637 ATOM 638 CG1 ILE A 84 46.762 37.810 87.791 1.00 0.00 xxxx 638 ATOM 639 CG2 ILE A 84 45.558 35.670 88.330 1.00 0.00 xxxx 639 ATOM 640 CD1 ILE A 84 45.500 38.666 87.830 1.00 0.00 xxxx 640 ATOM 641 N PRO A 85 48.091 33.178 87.706 1.00 0.00 xxxx 641 ATOM 642 CA PRO A 85 47.973 31.764 87.327 1.00 0.00 xxxx 642 ATOM 643 C PRO A 85 46.520 31.335 87.238 1.00 0.00 xxxx 643 ATOM 644 O PRO A 85 45.632 31.916 87.868 1.00 0.00 xxxx 644 ATOM 645 CB PRO A 85 48.674 31.022 88.473 1.00 0.00 xxxx 645 ATOM 646 CG PRO A 85 49.463 32.051 89.196 1.00 0.00 xxxx 646 ATOM 647 CD PRO A 85 48.742 33.353 89.015 1.00 0.00 xxxx 647 ATOM 648 N VAL A 86 46.274 30.286 86.454 1.00 0.00 xxxx 648 ATOM 649 CA VAL A 86 44.901 29.859 86.196 1.00 0.00 xxxx 649 ATOM 650 C VAL A 86 44.797 28.340 86.202 1.00 0.00 xxxx 650 ATOM 651 O VAL A 86 45.611 27.646 85.583 1.00 0.00 xxxx 651 ATOM 652 CB VAL A 86 44.352 30.464 84.890 1.00 0.00 xxxx 652 ATOM 653 CG1 VAL A 86 45.289 30.182 83.719 1.00 0.00 xxxx 653 ATOM 654 CG2 VAL A 86 42.942 29.968 84.607 1.00 0.00 xxxx 654 ATOM 655 N VAL A 87 43.791 27.823 86.898 1.00 0.00 xxxx 655 ATOM 656 CA VAL A 87 43.403 26.420 86.794 1.00 0.00 xxxx 656 ATOM 657 C VAL A 87 42.027 26.354 86.148 1.00 0.00 xxxx 657 ATOM 658 O VAL A 87 41.089 27.044 86.577 1.00 0.00 xxxx 658 ATOM 659 CB VAL A 87 43.467 25.691 88.150 1.00 0.00 xxxx 659 ATOM 660 CG1 VAL A 87 42.648 26.394 89.236 1.00 0.00 xxxx 660 ATOM 661 CG2 VAL A 87 43.054 24.220 87.999 1.00 0.00 xxxx 661 ATOM 662 N PHE A 88 41.928 25.582 85.072 1.00 0.00 xxxx 662 ATOM 663 CA PHE A 88 40.648 25.303 84.448 1.00 0.00 xxxx 663 ATOM 664 C PHE A 88 40.078 24.014 85.014 1.00 0.00 xxxx 664 ATOM 665 O PHE A 88 40.818 23.151 85.499 1.00 0.00 xxxx 665 ATOM 666 CB PHE A 88 40.792 25.194 82.930 1.00 0.00 xxxx 666 ATOM 667 CG PHE A 88 41.186 26.487 82.271 1.00 0.00 xxxx 667 ATOM 668 CD1 PHE A 88 42.515 26.781 82.032 1.00 0.00 xxxx 668 ATOM 669 CD2 PHE A 88 40.219 27.411 81.928 1.00 0.00 xxxx 669 ATOM 670 CE1 PHE A 88 42.878 27.966 81.428 1.00 0.00 xxxx 670 ATOM 671 CE2 PHE A 88 40.578 28.605 81.324 1.00 0.00 xxxx 671 ATOM 672 CZ PHE A 88 41.913 28.873 81.079 1.00 0.00 xxxx 672 ATOM 673 N PHE A 89 38.754 23.890 84.964 1.00 0.00 xxxx 673 ATOM 674 CA PHE A 89 38.138 22.676 85.482 1.00 0.00 xxxx 674 ATOM 675 C PHE A 89 36.867 22.330 84.727 1.00 0.00 xxxx 675 ATOM 676 O PHE A 89 36.149 23.222 84.267 1.00 0.00 xxxx 676 ATOM 677 CB PHE A 89 37.961 22.673 87.012 1.00 0.00 xxxx 677 ATOM 678 CG PHE A 89 37.089 23.782 87.578 1.00 0.00 xxxx 678 ATOM 679 CD1 PHE A 89 35.896 23.470 88.214 1.00 0.00 xxxx 679 ATOM 680 CD2 PHE A 89 37.503 25.112 87.565 1.00 0.00 xxxx 680 ATOM 681 CE1 PHE A 89 35.109 24.467 88.797 1.00 0.00 xxxx 681 ATOM 682 CE2 PHE A 89 36.706 26.122 88.140 1.00 0.00 xxxx 682 ATOM 683 CZ PHE A 89 35.519 25.786 88.760 1.00 0.00 xxxx 683 ATOM 684 N ASN A 90 36.640 21.017 84.573 1.00 0.00 xxxx 684 ATOM 685 CA ASN A 90 35.397 20.414 84.098 1.00 0.00 xxxx 685 ATOM 686 C ASN A 90 35.146 20.491 82.586 1.00 0.00 xxxx 686 ATOM 687 O ASN A 90 34.669 19.517 81.999 1.00 0.00 xxxx 687 ATOM 688 CB ASN A 90 34.186 20.871 84.920 1.00 0.00 xxxx 688 ATOM 689 CG ASN A 90 32.872 20.498 84.265 1.00 0.00 xxxx 689 ATOM 690 OD1 ASN A 90 32.284 21.310 83.565 1.00 0.00 xxxx 690 ATOM 691 ND2 ASN A 90 32.415 19.264 84.478 1.00 0.00 xxxx 691 ATOM 692 N LYS A 91 35.426 21.627 81.945 1.00 0.00 xxxx 692 ATOM 693 CA LYS A 91 35.463 21.697 80.485 1.00 0.00 xxxx 693 ATOM 694 C LYS A 91 36.912 21.923 80.081 1.00 0.00 xxxx 694 ATOM 695 O LYS A 91 37.547 22.880 80.539 1.00 0.00 xxxx 695 ATOM 696 CB LYS A 91 34.549 22.803 79.949 1.00 0.00 xxxx 696 ATOM 697 CG LYS A 91 33.064 22.644 80.345 1.00 0.00 xxxx 697 ATOM 698 CD LYS A 91 32.142 23.327 79.326 1.00 0.00 xxxx 698 ATOM 699 CE LYS A 91 30.781 23.654 79.916 1.00 0.00 xxxx 699 ATOM 700 NZ LYS A 91 29.882 24.261 78.901 1.00 0.00 xxxx 700 ATOM 701 N GLU A 92 37.437 21.027 79.254 1.00 0.00 xxxx 701 ATOM 702 CA GLU A 92 38.879 20.872 79.104 1.00 0.00 xxxx 702 ATOM 703 C GLU A 92 39.423 21.794 78.015 1.00 0.00 xxxx 703 ATOM 704 O GLU A 92 39.003 21.685 76.856 1.00 0.00 xxxx 704 ATOM 705 CB GLU A 92 39.200 19.429 78.753 1.00 0.00 xxxx 705 ATOM 706 CG GLU A 92 40.684 19.125 78.709 1.00 0.00 xxxx 706 ATOM 707 CD GLU A 92 40.980 17.677 78.380 1.00 0.00 xxxx 707 ATOM 708 OE1 GLU A 92 40.090 16.814 78.537 1.00 0.00 xxxx 708 ATOM 709 OE2 GLU A 92 42.114 17.396 77.934 1.00 0.00 xxxx 709 ATOM 710 N PRO A 93 40.368 22.684 78.324 1.00 0.00 xxxx 710 ATOM 711 CA PRO A 93 41.034 23.444 77.259 1.00 0.00 xxxx 711 ATOM 712 C PRO A 93 41.689 22.509 76.256 1.00 0.00 xxxx 712 ATOM 713 O PRO A 93 42.107 21.392 76.583 1.00 0.00 xxxx 713 ATOM 714 CB PRO A 93 42.093 24.257 78.012 1.00 0.00 xxxx 714 ATOM 715 CG PRO A 93 41.509 24.413 79.383 1.00 0.00 xxxx 715 ATOM 716 CD PRO A 93 40.824 23.096 79.663 1.00 0.00 xxxx 716 ATOM 717 N LEU A 94 41.800 22.993 75.024 1.00 0.00 xxxx 717 ATOM 718 CA LEU A 94 42.433 22.213 73.972 1.00 0.00 xxxx 718 ATOM 719 C LEU A 94 43.893 21.933 74.330 1.00 0.00 xxxx 719 ATOM 720 O LEU A 94 44.551 22.767 74.965 1.00 0.00 xxxx 720 ATOM 721 CB LEU A 94 42.347 22.978 72.650 1.00 0.00 xxxx 721 ATOM 722 CG LEU A 94 40.914 23.234 72.166 1.00 0.00 xxxx 722 ATOM 723 CD1 LEU A 94 40.921 24.250 71.041 1.00 0.00 xxxx 723 ATOM 724 CD2 LEU A 94 40.254 21.938 71.720 1.00 0.00 xxxx 724 ATOM 725 N PRO A 95 44.429 20.766 73.960 1.00 0.00 xxxx 725 ATOM 726 CA PRO A 95 45.799 20.416 74.381 1.00 0.00 xxxx 726 ATOM 727 C PRO A 95 46.854 21.452 74.020 1.00 0.00 xxxx 727 ATOM 728 O PRO A 95 47.771 21.701 74.817 1.00 0.00 xxxx 728 ATOM 729 CB PRO A 95 46.057 19.076 73.674 1.00 0.00 xxxx 729 ATOM 730 CG PRO A 95 44.717 18.514 73.408 1.00 0.00 xxxx 730 ATOM 731 CD PRO A 95 43.761 19.661 73.254 1.00 0.00 xxxx 731 ATOM 732 N GLU A 96 46.771 22.046 72.830 1.00 0.00 xxxx 732 ATOM 733 CA GLU A 96 47.793 23.013 72.448 1.00 0.00 xxxx 733 ATOM 734 C GLU A 96 47.633 24.324 73.203 1.00 0.00 xxxx 734 ATOM 735 O GLU A 96 48.621 25.037 73.416 1.00 0.00 xxxx 735 ATOM 736 CB GLU A 96 47.803 23.232 70.934 1.00 0.00 xxxx 736 ATOM 737 CG GLU A 96 48.235 22.015 70.147 1.00 0.00 xxxx 737 ATOM 738 CD GLU A 96 49.629 21.547 70.513 1.00 0.00 xxxx 738 ATOM 739 OE1 GLU A 96 50.534 22.401 70.614 1.00 0.00 xxxx 739 ATOM 740 OE2 GLU A 96 49.815 20.327 70.706 1.00 0.00 xxxx 740 ATOM 741 N ASP A 97 46.412 24.657 73.623 1.00 0.00 xxxx 741 ATOM 742 CA ASP A 97 46.227 25.848 74.446 1.00 0.00 xxxx 742 ATOM 743 C ASP A 97 46.855 25.669 75.824 1.00 0.00 xxxx 743 ATOM 744 O ASP A 97 47.407 26.621 76.384 1.00 0.00 xxxx 744 ATOM 745 CB ASP A 97 44.739 26.187 74.565 1.00 0.00 xxxx 745 ATOM 746 CG ASP A 97 44.180 26.845 73.303 1.00 0.00 xxxx 746 ATOM 747 OD1 ASP A 97 44.968 27.227 72.401 1.00 0.00 xxxx 747 ATOM 748 OD2 ASP A 97 42.939 27.003 73.227 1.00 0.00 xxxx 748 ATOM 749 N MET A 98 46.809 24.450 76.372 1.00 0.00 xxxx 749 ATOM 750 CA MET A 98 47.442 24.187 77.662 1.00 0.00 xxxx 750 ATOM 751 C MET A 98 48.953 24.408 77.626 1.00 0.00 xxxx 751 ATOM 752 O MET A 98 49.562 24.632 78.679 1.00 0.00 xxxx 752 ATOM 753 CB MET A 98 47.125 22.758 78.114 1.00 0.00 xxxx 753 ATOM 754 CG MET A 98 45.647 22.489 78.418 1.00 0.00 xxxx 754 ATOM 755 SD MET A 98 45.085 23.366 79.897 1.00 0.00 xxxx 755 ATOM 756 CE MET A 98 46.117 22.612 81.168 1.00 0.00 xxxx 756 ATOM 757 N LYS A 99 49.570 24.361 76.449 1.00 0.00 xxxx 757 ATOM 758 CA LYS A 99 51.007 24.541 76.305 1.00 0.00 xxxx 758 ATOM 759 C LYS A 99 51.424 26.004 76.175 1.00 0.00 xxxx 759 ATOM 760 O LYS A 99 52.622 26.282 76.069 1.00 0.00 xxxx 760 ATOM 761 CB LYS A 99 51.500 23.752 75.092 1.00 0.00 xxxx 761 ATOM 762 CG LYS A 99 51.309 22.254 75.227 1.00 0.00 xxxx 762 ATOM 763 CD LYS A 99 51.695 21.541 73.938 1.00 0.00 xxxx 763 ATOM 764 CE LYS A 99 51.555 20.033 74.071 1.00 0.00 xxxx 764 ATOM 765 NZ LYS A 99 52.567 19.465 75.004 1.00 0.00 xxxx 765 ATOM 766 N LYS A 100 50.472 26.942 76.211 1.00 0.00 xxxx 766 ATOM 767 CA LYS A 100 50.794 28.352 76.012 1.00 0.00 xxxx 767 ATOM 768 C LYS A 100 51.533 28.962 77.197 1.00 0.00 xxxx 768 ATOM 769 O LYS A 100 52.212 29.977 77.025 1.00 0.00 xxxx 769 ATOM 770 CB LYS A 100 49.513 29.152 75.759 1.00 0.00 xxxx 770 ATOM 771 CG LYS A 100 48.831 28.827 74.448 1.00 0.00 xxxx 771 ATOM 772 CD LYS A 100 47.377 29.291 74.441 1.00 0.00 xxxx 772 ATOM 773 CE LYS A 100 47.258 30.796 74.398 1.00 0.00 xxxx 773 ATOM 774 NZ LYS A 100 47.635 31.353 73.062 1.00 0.00 xxxx 774 ATOM 775 N TRP A 101 51.406 28.382 78.391 1.00 0.00 xxxx 775 ATOM 776 CA TRP A 101 52.010 28.966 79.579 1.00 0.00 xxxx 776 ATOM 777 C TRP A 101 52.277 27.853 80.580 1.00 0.00 xxxx 777 ATOM 778 O TRP A 101 51.626 26.806 80.555 1.00 0.00 xxxx 778 ATOM 779 CB TRP A 101 51.056 29.999 80.188 1.00 0.00 xxxx 779 ATOM 780 CG TRP A 101 51.640 30.945 81.199 1.00 0.00 xxxx 780 ATOM 781 CD1 TRP A 101 52.949 31.320 81.335 1.00 0.00 xxxx 781 ATOM 782 CD2 TRP A 101 50.912 31.647 82.215 1.00 0.00 xxxx 782 ATOM 783 NE1 TRP A 101 53.078 32.218 82.377 1.00 0.00 xxxx 783 ATOM 784 CE2 TRP A 101 51.842 32.434 82.930 1.00 0.00 xxxx 784 ATOM 785 CE3 TRP A 101 49.561 31.694 82.582 1.00 0.00 xxxx 785 ATOM 786 CZ2 TRP A 101 51.464 33.257 83.995 1.00 0.00 xxxx 786 ATOM 787 CZ3 TRP A 101 49.188 32.507 83.645 1.00 0.00 xxxx 787 ATOM 788 CH2 TRP A 101 50.136 33.277 84.336 1.00 0.00 xxxx 788 ATOM 789 N ASP A 102 53.224 28.102 81.483 1.00 0.00 xxxx 789 ATOM 790 CA ASP A 102 53.626 27.126 82.488 1.00 0.00 xxxx 790 ATOM 791 C ASP A 102 52.973 27.364 83.847 1.00 0.00 xxxx 791 ATOM 792 O ASP A 102 53.411 26.777 84.842 1.00 0.00 xxxx 792 ATOM 793 CB ASP A 102 55.155 27.039 82.598 1.00 0.00 xxxx 793 ATOM 794 CG ASP A 102 55.797 28.340 83.059 1.00 0.00 xxxx 794 ATOM 795 OD1 ASP A 102 55.124 29.388 83.125 1.00 0.00 xxxx 795 ATOM 796 OD2 ASP A 102 57.013 28.310 83.351 1.00 0.00 xxxx 796 ATOM 797 N LYS A 103 51.950 28.211 83.912 1.00 0.00 xxxx 797 ATOM 798 CA LYS A 103 51.156 28.402 85.119 1.00 0.00 xxxx 798 ATOM 799 C LYS A 103 49.689 28.099 84.858 1.00 0.00 xxxx 799 ATOM 800 O LYS A 103 48.798 28.736 85.427 1.00 0.00 xxxx 800 ATOM 801 CB LYS A 103 51.366 29.804 85.695 1.00 0.00 xxxx 801 ATOM 802 CG LYS A 103 52.824 30.084 86.062 1.00 0.00 xxxx 802 ATOM 803 CD LYS A 103 52.960 31.395 86.808 1.00 0.00 xxxx 803 ATOM 804 CE LYS A 103 54.412 31.709 87.110 1.00 0.00 xxxx 804 ATOM 805 NZ LYS A 103 54.516 32.987 87.861 1.00 0.00 xxxx 805 ATOM 806 N VAL A 104 49.422 27.112 83.996 1.00 0.00 xxxx 806 ATOM 807 CA VAL A 104 48.073 26.720 83.609 1.00 0.00 xxxx 807 ATOM 808 C VAL A 104 47.869 25.249 83.945 1.00 0.00 xxxx 808 ATOM 809 O VAL A 104 48.705 24.411 83.596 1.00 0.00 xxxx 809 ATOM 810 CB VAL A 104 47.826 26.956 82.111 1.00 0.00 xxxx 810 ATOM 811 CG1 VAL A 104 46.404 26.572 81.757 1.00 0.00 xxxx 811 ATOM 812 CG2 VAL A 104 48.111 28.418 81.741 1.00 0.00 xxxx 812 ATOM 813 N TYR A 105 46.758 24.943 84.611 1.00 0.00 xxxx 813 ATOM 814 CA TYR A 105 46.428 23.587 85.034 1.00 0.00 xxxx 814 ATOM 815 C TYR A 105 45.001 23.257 84.625 1.00 0.00 xxxx 815 ATOM 816 O TYR A 105 44.203 24.138 84.306 1.00 0.00 xxxx 816 ATOM 817 CB TYR A 105 46.590 23.433 86.558 1.00 0.00 xxxx 817 ATOM 818 CG TYR A 105 48.029 23.536 86.975 1.00 0.00 xxxx 818 ATOM 819 CD1 TYR A 105 48.641 24.778 87.146 1.00 0.00 xxxx 819 ATOM 820 CD2 TYR A 105 48.805 22.395 87.140 1.00 0.00 xxxx 820 ATOM 821 CE1 TYR A 105 49.989 24.873 87.485 1.00 0.00 xxxx 821 ATOM 822 CE2 TYR A 105 50.146 22.478 87.485 1.00 0.00 xxxx 822 ATOM 823 CZ TYR A 105 50.737 23.719 87.661 1.00 0.00 xxxx 823 ATOM 824 OH TYR A 105 52.074 23.794 87.999 1.00 0.00 xxxx 824 ATOM 825 N TYR A 106 44.671 21.959 84.666 1.00 0.00 xxxx 825 ATOM 826 CA TYR A 106 43.319 21.482 84.412 1.00 0.00 xxxx 826 ATOM 827 C TYR A 106 42.980 20.374 85.400 1.00 0.00 xxxx 827 ATOM 828 O TYR A 106 43.782 19.459 85.601 1.00 0.00 xxxx 828 ATOM 829 CB TYR A 106 43.141 20.937 82.973 1.00 0.00 xxxx 829 ATOM 830 CG TYR A 106 41.739 20.422 82.780 1.00 0.00 xxxx 830 ATOM 831 CD1 TYR A 106 40.675 21.304 82.676 1.00 0.00 xxxx 831 ATOM 832 CD2 TYR A 106 41.455 19.050 82.778 1.00 0.00 xxxx 832 ATOM 833 CE1 TYR A 106 39.369 20.857 82.542 1.00 0.00 xxxx 833 ATOM 834 CE2 TYR A 106 40.142 18.593 82.648 1.00 0.00 xxxx 834 ATOM 835 CZ TYR A 106 39.107 19.497 82.522 1.00 0.00 xxxx 835 ATOM 836 OH TYR A 106 37.803 19.075 82.396 1.00 0.00 xxxx 836 ATOM 837 N VAL A 107 41.773 20.428 85.968 1.00 0.00 xxxx 837 ATOM 838 CA VAL A 107 41.248 19.379 86.842 1.00 0.00 xxxx 838 ATOM 839 C VAL A 107 39.975 18.819 86.226 1.00 0.00 xxxx 839 ATOM 840 O VAL A 107 39.050 19.574 85.900 1.00 0.00 xxxx 840 ATOM 841 CB VAL A 107 40.951 19.903 88.259 1.00 0.00 xxxx 841 ATOM 842 CG1 VAL A 107 40.361 18.800 89.114 1.00 0.00 xxxx 842 ATOM 843 CG2 VAL A 107 42.213 20.446 88.908 1.00 0.00 xxxx 843 ATOM 844 N GLY A 108 39.915 17.493 86.100 1.00 0.00 xxxx 844 ATOM 845 CA GLY A 108 38.702 16.866 85.622 1.00 0.00 xxxx 845 ATOM 846 C GLY A 108 38.800 15.365 85.755 1.00 0.00 xxxx 846 ATOM 847 O GLY A 108 39.295 14.851 86.763 1.00 0.00 xxxx 847 ATOM 848 N ALA A 109 38.332 14.650 84.743 1.00 0.00 xxxx 848 ATOM 849 CA ALA A 109 38.287 13.200 84.787 1.00 0.00 xxxx 849 ATOM 850 C ALA A 109 38.364 12.689 83.362 1.00 0.00 xxxx 850 ATOM 851 O ALA A 109 38.064 13.415 82.414 1.00 0.00 xxxx 851 ATOM 852 CB ALA A 109 37.007 12.726 85.481 1.00 0.00 xxxx 852 ATOM 853 N LYS A 110 38.779 11.435 83.217 1.00 0.00 xxxx 853 ATOM 854 CA LYS A 110 38.965 10.850 81.892 1.00 0.00 xxxx 854 ATOM 855 C LYS A 110 37.616 10.372 81.379 1.00 0.00 xxxx 855 ATOM 856 O LYS A 110 37.135 9.308 81.764 1.00 0.00 xxxx 856 ATOM 857 CB LYS A 110 39.942 9.684 81.966 1.00 0.00 xxxx 857 ATOM 858 CG LYS A 110 41.382 10.111 82.235 1.00 0.00 xxxx 858 ATOM 859 CD LYS A 110 41.886 11.014 81.116 1.00 0.00 xxxx 859 ATOM 860 CE LYS A 110 43.406 11.034 81.063 1.00 0.00 xxxx 860 ATOM 861 NZ LYS A 110 43.975 9.730 80.625 1.00 0.00 xxxx 861 ATOM 862 N ALA A 111 37.021 11.140 80.467 1.00 0.00 xxxx 862 ATOM 863 CA ALA A 111 35.667 10.836 80.021 1.00 0.00 xxxx 863 ATOM 864 C ALA A 111 35.566 9.462 79.362 1.00 0.00 xxxx 864 ATOM 865 O ALA A 111 34.507 8.820 79.423 1.00 0.00 xxxx 865 ATOM 866 CB ALA A 111 35.170 11.933 79.076 1.00 0.00 xxxx 866 ATOM 867 N GLU A 112 36.657 9.000 78.744 1.00 0.00 xxxx 867 ATOM 868 CA GLU A 112 36.709 7.645 78.202 1.00 0.00 xxxx 868 ATOM 869 C GLU A 112 36.330 6.615 79.255 1.00 0.00 xxxx 869 ATOM 870 O GLU A 112 35.572 5.675 78.978 1.00 0.00 xxxx 870 ATOM 871 CB GLU A 112 38.121 7.355 77.686 1.00 0.00 xxxx 871 ATOM 872 CG GLU A 112 38.618 8.313 76.606 1.00 0.00 xxxx 872 ATOM 873 CD GLU A 112 39.455 9.466 77.141 1.00 0.00 xxxx 873 ATOM 874 OE1 GLU A 112 39.153 10.008 78.232 1.00 0.00 xxxx 874 ATOM 875 OE2 GLU A 112 40.432 9.841 76.453 1.00 0.00 xxxx 875 ATOM 876 N GLN A 113 36.855 6.776 80.473 1.00 0.00 xxxx 876 ATOM 877 CA GLN A 113 36.564 5.823 81.540 1.00 0.00 xxxx 877 ATOM 878 C GLN A 113 35.081 5.814 81.880 1.00 0.00 xxxx 878 ATOM 879 O GLN A 113 34.488 4.748 82.097 1.00 0.00 xxxx 879 ATOM 880 CB GLN A 113 37.402 6.166 82.776 1.00 0.00 xxxx 880 ATOM 881 CG GLN A 113 37.058 5.368 84.034 1.00 0.00 xxxx 881 ATOM 882 CD GLN A 113 37.890 5.767 85.260 1.00 0.00 xxxx 882 ATOM 883 OE1 GLN A 113 38.035 6.954 85.590 1.00 0.00 xxxx 883 ATOM 884 NE2 GLN A 113 38.439 4.765 85.941 1.00 0.00 xxxx 884 ATOM 885 N SER A 114 34.455 6.990 81.911 1.00 0.00 xxxx 885 ATOM 886 CA SER A 114 33.031 7.032 82.216 1.00 0.00 xxxx 886 ATOM 887 C SER A 114 32.215 6.359 81.116 1.00 0.00 xxxx 887 ATOM 888 O SER A 114 31.241 5.660 81.410 1.00 0.00 xxxx 888 ATOM 889 CB SER A 114 32.564 8.459 82.527 1.00 0.00 xxxx 889 ATOM 890 OG SER A 114 32.609 9.317 81.402 1.00 0.00 xxxx 890 ATOM 891 N GLY A 115 32.617 6.521 79.848 1.00 0.00 xxxx 891 ATOM 892 CA GLY A 115 31.920 5.842 78.762 1.00 0.00 xxxx 892 ATOM 893 C GLY A 115 32.049 4.333 78.862 1.00 0.00 xxxx 893 ATOM 894 O GLY A 115 31.061 3.602 78.700 1.00 0.00 xxxx 894 ATOM 895 N ILE A 116 33.252 3.848 79.163 1.00 0.00 xxxx 895 ATOM 896 CA ILE A 116 33.454 2.405 79.314 1.00 0.00 xxxx 896 ATOM 897 C ILE A 116 32.591 1.865 80.443 1.00 0.00 xxxx 897 ATOM 898 O ILE A 116 31.934 0.825 80.301 1.00 0.00 xxxx 898 ATOM 899 CB ILE A 116 34.940 2.081 79.537 1.00 0.00 xxxx 899 ATOM 900 CG1 ILE A 116 35.755 2.410 78.283 1.00 0.00 xxxx 900 ATOM 901 CG2 ILE A 116 35.112 0.620 79.957 1.00 0.00 xxxx 901 ATOM 902 CD1 ILE A 116 37.259 2.474 78.545 1.00 0.00 xxxx 902 ATOM 903 N LEU A 117 32.590 2.549 81.588 1.00 0.00 xxxx 903 ATOM 904 CA LEU A 117 31.816 2.045 82.721 1.00 0.00 xxxx 904 ATOM 905 C LEU A 117 30.326 2.034 82.407 1.00 0.00 xxxx 905 ATOM 906 O LEU A 117 29.605 1.110 82.800 1.00 0.00 xxxx 906 ATOM 907 CB LEU A 117 32.116 2.869 83.974 1.00 0.00 xxxx 907 ATOM 908 CG LEU A 117 33.569 2.740 84.443 1.00 0.00 xxxx 908 ATOM 909 CD1 LEU A 117 33.871 3.740 85.536 1.00 0.00 xxxx 909 ATOM 910 CD2 LEU A 117 33.858 1.322 84.933 1.00 0.00 xxxx 910 ATOM 911 N GLN A 118 29.852 3.033 81.669 1.00 0.00 xxxx 911 ATOM 912 CA GLN A 118 28.444 3.055 81.301 1.00 0.00 xxxx 912 ATOM 913 C GLN A 118 28.099 1.925 80.332 1.00 0.00 xxxx 913 ATOM 914 O GLN A 118 27.021 1.323 80.431 1.00 0.00 xxxx 914 ATOM 915 CB GLN A 118 28.100 4.415 80.706 1.00 0.00 xxxx 915 ATOM 916 CG GLN A 118 26.672 4.525 80.317 1.00 0.00 xxxx 916 ATOM 917 CD GLN A 118 26.359 5.813 79.604 1.00 0.00 xxxx 917 ATOM 918 OE1 GLN A 118 26.587 5.942 78.406 1.00 0.00 xxxx 918 ATOM 919 NE2 GLN A 118 25.821 6.774 80.339 1.00 0.00 xxxx 919 ATOM 920 N GLY A 119 28.997 1.622 79.391 1.00 0.00 xxxx 920 ATOM 921 CA GLY A 119 28.759 0.516 78.490 1.00 0.00 xxxx 921 ATOM 922 C GLY A 119 28.777 −0.821 79.199 1.00 0.00 xxxx 922 ATOM 923 O GLY A 119 28.010 −1.722 78.851 1.00 0.00 xxxx 923 ATOM 924 N GLN A 120 29.643 −0.969 80.210 1.00 0.00 xxxx 924 ATOM 925 CA GLN A 120 29.658 −2.210 80.978 1.00 0.00 xxxx 925 ATOM 926 C GLN A 120 28.335 −2.435 81.700 1.00 0.00 xxxx 926 ATOM 927 O GLN A 120 27.832 −3.566 81.743 1.00 0.00 xxxx 927 ATOM 928 CB GLN A 120 30.821 −2.219 81.964 1.00 0.00 xxxx 928 ATOM 929 CG GLN A 120 32.178 −2.283 81.299 1.00 0.00 xxxx 929 ATOM 930 CD GLN A 120 33.308 −2.245 82.300 1.00 0.00 xxxx 930 ATOM 931 OE1 GLN A 120 33.092 −2.012 83.493 1.00 0.00 xxxx 931 ATOM 932 NE2 GLN A 120 34.526 −2.486 81.827 1.00 0.00 xxxx 932 ATOM 933 N ILE A 121 27.765 −1.384 82.289 1.00 0.00 xxxx 933 ATOM 934 CA ILE A 121 26.481 −1.522 82.973 1.00 0.00 xxxx 934 ATOM 935 C ILE A 121 25.433 −2.060 82.012 1.00 0.00 xxxx 935 ATOM 936 O ILE A 121 24.703 −3.015 82.318 1.00 0.00 xxxx 936 ATOM 937 CB ILE A 121 26.044 −0.170 83.567 1.00 0.00 xxxx 937 ATOM 938 CG1 ILE A 121 26.980 0.263 84.696 1.00 0.00 xxxx 938 ATOM 939 CG2 ILE A 121 24.601 −0.259 84.071 1.00 0.00 xxxx 939 ATOM 940 CD1 ILE A 121 26.783 1.722 85.103 1.00 0.00 xxxx 940 ATOM 941 N MET A 122 25.338 −1.450 80.831 1.00 0.00 xxxx 941 ATOM 942 CA MET A 122 24.306 −1.857 79.886 1.00 0.00 xxxx 942 ATOM 943 C MET A 122 24.573 −3.252 79.344 1.00 0.00 xxxx 943 ATOM 944 O MET A 122 23.640 −4.049 79.180 1.00 0.00 xxxx 944 ATOM 945 CB MET A 122 24.209 −0.852 78.742 1.00 0.00 xxxx 945 ATOM 946 CG MET A 122 23.000 −1.108 77.851 1.00 0.00 xxxx 946 ATOM 947 SD MET A 122 21.435 −0.672 78.643 1.00 0.00 xxxx 947 ATOM 948 CE MET A 122 21.453 1.110 78.453 1.00 0.00 xxxx 948 ATOM 949 N ALA A 123 25.839 −3.564 79.049 1.00 0.00 xxxx 949 ATOM 950 CA ALA A 123 26.157 −4.867 78.473 1.00 0.00 xxxx 950 ATOM 951 C ALA A 123 25.888 −5.980 79.471 1.00 0.00 xxxx 951 ATOM 952 O ALA A 123 25.370 −7.043 79.104 1.00 0.00 xxxx 952 ATOM 953 CB ALA A 123 27.618 −4.898 78.014 1.00 0.00 xxxx 953 ATOM 954 N ASP A 124 26.216 −5.746 80.744 1.00 0.00 xxxx 954 ATOM 955 CA ASP A 124 25.959 −6.760 81.759 1.00 0.00 xxxx 955 ATOM 956 C ASP A 124 24.465 −6.967 81.961 1.00 0.00 xxxx 956 ATOM 957 O ASP A 124 24.005 −8.103 82.152 1.00 0.00 xxxx 957 ATOM 958 CB ASP A 124 26.654 −6.386 83.067 1.00 0.00 xxxx 958 ATOM 959 CG ASP A 124 28.160 −6.575 82.996 1.00 0.00 xxxx 959 ATOM 960 OD1 ASP A 124 28.633 −7.287 82.084 1.00 0.00 xxxx 960 ATOM 961 OD2 ASP A 124 28.877 −6.021 83.851 1.00 0.00 xxxx 961 ATOM 962 N TYR A 125 23.681 −5.890 81.898 1.00 0.00 xxxx 962 ATOM 963 CA TYR A 125 22.236 −6.059 81.995 1.00 0.00 xxxx 963 ATOM 964 C TYR A 125 21.709 −6.872 80.819 1.00 0.00 xxxx 964 ATOM 965 O TYR A 125 20.909 −7.803 80.994 1.00 0.00 xxxx 965 ATOM 966 CB TYR A 125 21.544 −4.692 82.073 1.00 0.00 xxxx 966 ATOM 967 CG TYR A 125 20.049 −4.820 81.878 1.00 0.00 xxxx 967 ATOM 968 CD1 TYR A 125 19.209 −5.126 82.944 1.00 0.00 xxxx 968 ATOM 969 CD2 TYR A 125 19.487 −4.695 80.614 1.00 0.00 xxxx 969 ATOM 970 CE1 TYR A 125 17.838 −5.281 82.746 1.00 0.00 xxxx 970 ATOM 971 CE2 TYR A 125 18.132 −4.858 80.411 1.00 0.00 xxxx 971 ATOM 972 CZ TYR A 125 17.323 −5.140 81.472 1.00 0.00 xxxx 972 ATOM 973 OH TYR A 125 15.974 −5.294 81.249 1.00 0.00 xxxx 973 ATOM 974 N TRP A 126 22.144 −6.522 79.607 1.00 0.00 xxxx 974 ATOM 975 CA TRP A 126 21.697 −7.212 78.402 1.00 0.00 xxxx 975 ATOM 976 C TRP A 126 21.984 −8.704 78.489 1.00 0.00 xxxx 976 ATOM 977 O TRP A 126 21.119 −9.535 78.184 1.00 0.00 xxxx 977 ATOM 978 CB TRP A 126 22.395 −6.598 77.184 1.00 0.00 xxxx 978 ATOM 979 CG TRP A 126 22.086 −7.259 75.841 1.00 0.00 xxxx 979 ATOM 980 CD1 TRP A 126 22.802 −8.247 75.234 1.00 0.00 xxxx 980 ATOM 981 CD2 TRP A 126 21.009 −6.938 74.949 1.00 0.00 xxxx 981 ATOM 982 NE1 TRP A 126 22.229 −8.578 74.023 1.00 0.00 xxxx 982 ATOM 983 CE2 TRP A 126 21.131 −7.782 73.827 1.00 0.00 xxxx 983 ATOM 984 CE3 TRP A 126 19.953 −6.027 74.995 1.00 0.00 xxxx 984 ATOM 985 CZ2 TRP A 126 20.231 −7.746 72.762 1.00 0.00 xxxx 985 ATOM 986 CZ3 TRP A 126 19.054 −5.988 73.925 1.00 0.00 xxxx 986 ATOM 987 CH2 TRP A 126 19.206 −6.841 72.832 1.00 0.00 xxxx 987 ATOM 988 N LYS A 127 23.197 −9.063 78.918 1.00 0.00 xxxx 988 ATOM 989 CA LYS A 127 23.576 −10.473 78.961 1.00 0.00 xxxx 989 ATOM 990 C LYS A 127 22.768 −11.247 79.995 1.00 0.00 xxxx 990 ATOM 991 O LYS A 127 22.540 −12.453 79.826 1.00 0.00 xxxx 991 ATOM 992 CB LYS A 127 25.073 −10.596 79.250 1.00 0.00 xxxx 992 ATOM 993 CG LYS A 127 25.956 −10.147 78.103 1.00 0.00 xxxx 993 ATOM 994 CD LYS A 127 27.414 −10.102 78.521 1.00 0.00 xxxx 994 ATOM 995 CE LYS A 127 28.307 −9.804 77.331 1.00 0.00 xxxx 995 ATOM 996 NZ LYS A 127 29.742 −9.750 77.743 1.00 0.00 xxxx 996 ATOM 997 N ALA A 128 22.332 −10.583 81.067 1.00 0.00 xxxx 997 ATOM 998 CA ALA A 128 21.615 −11.253 82.147 1.00 0.00 xxxx 998 ATOM 999 C ALA A 128 20.110 −11.293 81.937 1.00 0.00 xxxx 999 ATOM 1000 O ALA A 128 19.420 −12.022 82.657 1.00 0.00 xxxx 1000 ATOM 1001 CB ALA A 128 21.898 −10.540 83.473 1.00 0.00 xxxx 1001 ATOM 1002 N HIS A 129 19.583 −10.530 80.984 1.00 0.00 xxxx 1002 ATOM 1003 CA HIS A 129 18.139 −10.395 80.799 1.00 0.00 xxxx 1003 ATOM 1004 C HIS A 129 17.763 −10.624 79.343 1.00 0.00 xxxx 1004 ATOM 1005 O HIS A 129 17.662 −9.671 78.558 1.00 0.00 xxxx 1005 ATOM 1006 CB HIS A 129 17.662 −9.033 81.295 1.00 0.00 xxxx 1006 ATOM 1007 CG HIS A 129 17.943 −8.800 82.743 1.00 0.00 xxxx 1007 ATOM 1008 ND1 HIS A 129 17.015 −9.057 83.730 1.00 0.00 xxxx 1008 ATOM 1009 CD2 HIS A 129 19.060 −8.370 83.377 1.00 0.00 xxxx 1009 ATOM 1010 CE1 HIS A 129 17.544 −8.781 84.909 1.00 0.00 xxxx 1010 ATOM 1011 NE2 HIS A 129 18.782 −8.363 84.723 1.00 0.00 xxxx 1011 ATOM 1012 N PRO A 130 17.512 −11.875 78.955 1.00 0.00 xxxx 1012 ATOM 1013 CA PRO A 130 17.138 −12.147 77.556 1.00 0.00 xxxx 1013 ATOM 1014 C PRO A 130 15.891 −11.409 77.117 1.00 0.00 xxxx 1014 ATOM 1015 O PRO A 130 15.751 −11.087 75.930 1.00 0.00 xxxx 1015 ATOM 1016 CB PRO A 130 16.922 −13.667 77.532 1.00 0.00 xxxx 1016 ATOM 1017 CG PRO A 130 17.575 −14.187 78.772 1.00 0.00 xxxx 1017 ATOM 1018 CD PRO A 130 17.522 −13.090 79.785 1.00 0.00 xxxx 1018 ATOM 1019 N GLU A 131 14.981 −11.120 78.046 1.00 0.00 xxxx 1019 ATOM 1020 CA GLU A 131 13.760 −10.409 77.702 1.00 0.00 xxxx 1020 ATOM 1021 C GLU A 131 14.022 −8.977 77.257 1.00 0.00 xxxx 1021 ATOM 1022 O GLU A 131 13.108 −8.337 76.722 1.00 0.00 xxxx 1022 ATOM 1023 CB GLU A 131 12.791 −10.429 78.885 1.00 0.00 xxxx 1023 ATOM 1024 CG GLU A 131 13.175 −9.489 80.025 1.00 0.00 xxxx 1024 ATOM 1025 CD GLU A 131 14.111 −10.120 81.050 1.00 0.00 xxxx 1025 ATOM 1026 OE1 GLU A 131 14.789 −11.127 80.739 1.00 0.00 xxxx 1026 ATOM 1027 OE2 GLU A 131 14.164 −9.598 82.186 1.00 0.00 xxxx 1027 ATOM 1028 N ALA A 132 15.240 −8.470 77.452 1.00 0.00 xxxx 1028 ATOM 1029 CA ALA A 132 15.558 −7.112 77.019 1.00 0.00 xxxx 1029 ATOM 1030 C ALA A 132 15.533 −6.981 75.502 1.00 0.00 xxxx 1030 ATOM 1031 O ALA A 132 15.259 −5.893 74.977 1.00 0.00 xxxx 1031 ATOM 1032 CB ALA A 132 16.920 −6.693 77.571 1.00 0.00 xxxx 1032 ATOM 1033 N ASP A 133 15.820 −8.070 74.788 1.00 0.00 xxxx 1033 ATOM 1034 CA ASP A 133 15.782 −8.100 73.326 1.00 0.00 xxxx 1034 ATOM 1035 C ASP A 133 14.326 −8.311 72.915 1.00 0.00 xxxx 1035 ATOM 1036 O ASP A 133 13.884 −9.410 72.571 1.00 0.00 xxxx 1036 ATOM 1037 CB ASP A 133 16.710 −9.194 72.816 1.00 0.00 xxxx 1037 ATOM 1038 CG ASP A 133 16.793 −9.243 71.311 1.00 0.00 xxxx 1038 ATOM 1039 OD1 ASP A 133 16.448 −8.238 70.665 1.00 0.00 xxxx 1039 ATOM 1040 OD2 ASP A 133 17.207 −10.292 70.769 1.00 0.00 xxxx 1040 ATOM 1041 N LYS A 134 13.564 −7.217 72.960 1.00 0.00 xxxx 1041 ATOM 1042 CA LYS A 134 12.112 −7.327 72.850 1.00 0.00 xxxx 1042 ATOM 1043 C LYS A 134 11.679 −7.919 71.514 1.00 0.00 xxxx 1043 ATOM 1044 O LYS A 134 10.719 −8.697 71.460 1.00 0.00 xxxx 1044 ATOM 1045 CB LYS A 134 11.446 −5.975 73.106 1.00 0.00 xxxx 1045 ATOM 1046 CG LYS A 134 11.290 −5.645 74.582 1.00 0.00 xxxx 1046 ATOM 1047 CD LYS A 134 10.626 −4.292 74.777 1.00 0.00 xxxx 1047 ATOM 1048 CE LYS A 134 11.499 −3.172 74.246 1.00 0.00 xxxx 1048 ATOM 1049 NZ LYS A 134 10.924 −1.840 74.594 1.00 0.00 xxxx 1049 ATOM 1050 N ASN A 135 12.370 −7.572 70.428 1.00 0.00 xxxx 1050 ATOM 1051 CA ASN A 135 11.992 −8.084 69.112 1.00 0.00 xxxx 1051 ATOM 1052 C ASN A 135 12.741 −9.357 68.735 1.00 0.00 xxxx 1052 ATOM 1053 O ASN A 135 12.604 −9.833 67.603 1.00 0.00 xxxx 1053 ATOM 1054 CB ASN A 135 12.122 −7.014 68.020 1.00 0.00 xxxx 1054 ATOM 1055 CG ASN A 135 13.561 −6.704 67.666 1.00 0.00 xxxx 1055 ATOM 1056 OD1 ASN A 135 14.467 −6.947 68.452 1.00 0.00 xxxx 1056 ATOM 1057 ND2 ASN A 135 13.774 −6.149 66.479 1.00 0.00 xxxx 1057 ATOM 1058 N HIS A 136 13.522 −9.917 69.662 1.00 0.00 xxxx 1058 ATOM 1059 CA HIS A 136 14.134 −11.237 69.512 1.00 0.00 xxxx 1059 ATOM 1060 C HIS A 136 15.038 −11.338 68.285 1.00 0.00 xxxx 1060 ATOM 1061 O HIS A 136 15.151 −12.405 67.677 1.00 0.00 xxxx 1061 ATOM 1062 CB HIS A 136 13.080 −12.350 69.509 1.00 0.00 xxxx 1062 ATOM 1063 CG HIS A 136 12.084 −12.240 70.621 1.00 0.00 xxxx 1063 ATOM 1064 ND1 HIS A 136 12.436 −12.352 71.949 1.00 0.00 xxxx 1064 ATOM 1065 CD2 HIS A 136 10.746 −12.032 70.602 1.00 0.00 xxxx 1065 ATOM 1066 CE1 HIS A 136 11.358 −12.214 72.701 1.00 0.00 xxxx 1066 ATOM 1067 NE2 HIS A 136 10.319 −12.020 71.908 1.00 0.00 xxxx 1067 ATOM 1068 N ASP A 137 15.700 −10.243 67.908 1.00 0.00 xxxx 1068 ATOM 1069 CA ASP A 137 16.562 −10.248 66.733 1.00 0.00 xxxx 1069 ATOM 1070 C ASP A 137 18.042 −10.399 67.064 1.00 0.00 xxxx 1070 ATOM 1071 O ASP A 137 18.867 −10.406 66.145 1.00 0.00 xxxx 1071 ATOM 1072 CB ASP A 137 16.307 −9.015 65.842 1.00 0.00 xxxx 1072 ATOM 1073 CG ASP A 137 16.759 −7.702 66.476 1.00 0.00 xxxx 1073 ATOM 1074 OD1 ASP A 137 17.124 −7.680 67.671 1.00 0.00 xxxx 1074 ATOM 1075 OD2 ASP A 137 16.738 −6.676 65.760 1.00 0.00 xxxx 1075 ATOM 1076 N GLY A 138 18.398 −10.520 68.345 1.00 0.00 xxxx 1076 ATOM 1077 CA GLY A 138 19.792 −10.644 68.720 1.00 0.00 xxxx 1077 ATOM 1078 C GLY A 138 20.591 −9.366 68.624 1.00 0.00 xxxx 1078 ATOM 1079 O GLY A 138 21.826 −9.417 68.631 1.00 0.00 xxxx 1079 ATOM 1080 N VAL A 139 19.923 −8.221 68.520 1.00 0.00 xxxx 1080 ATOM 1081 CA VAL A 139 20.562 −6.922 68.351 1.00 0.00 xxxx 1081 ATOM 1082 C VAL A 139 19.945 −5.964 69.360 1.00 0.00 xxxx 1082 ATOM 1083 O VAL A 139 18.726 −5.970 69.560 1.00 0.00 xxxx 1083 ATOM 1084 CB VAL A 139 20.342 −6.386 66.917 1.00 0.00 xxxx 1084 ATOM 1085 CG1 VAL A 139 20.987 −5.023 66.742 1.00 0.00 xxxx 1085 ATOM 1086 CG2 VAL A 139 20.877 −7.353 65.882 1.00 0.00 xxxx 1086 ATOM 1087 N MET A 140 20.775 −5.124 69.979 1.00 0.00 xxxx 1087 ATOM 1088 CA MET A 140 20.291 −4.122 70.927 1.00 0.00 xxxx 1088 ATOM 1089 C MET A 140 19.945 −2.835 70.175 1.00 0.00 xxxx 1089 ATOM 1090 O MET A 140 20.842 −2.119 69.723 1.00 0.00 xxxx 1090 ATOM 1091 CB MET A 140 21.358 −3.856 71.989 1.00 0.00 xxxx 1091 ATOM 1092 CG MET A 140 21.000 −2.732 72.964 1.00 0.00 xxxx 1092 ATOM 1093 SD MET A 140 22.400 −2.094 73.929 1.00 0.00 xxxx 1093 ATOM 1094 CE MET A 140 22.726 −3.488 74.998 1.00 0.00 xxxx 1094 ATOM 1095 N GLN A 141 18.650 −2.525 70.064 1.00 0.00 xxxx 1095 ATOM 1096 CA GLN A 141 18.204 −1.251 69.491 1.00 0.00 xxxx 1096 ATOM 1097 C GLN A 141 18.274 −0.171 70.563 1.00 0.00 xxxx 1097 ATOM 1098 O GLN A 141 17.623 −0.295 71.606 1.00 0.00 xxxx 1098 ATOM 1099 CB GLN A 141 16.764 −1.368 68.989 1.00 0.00 xxxx 1099 ATOM 1100 CG GLN A 141 16.604 −1.910 67.573 1.00 0.00 xxxx 1100 ATOM 1101 CD GLN A 141 16.779 −3.409 67.477 1.00 0.00 xxxx 1101 ATOM 1102 OE1 GLN A 141 16.319 −4.156 68.337 1.00 0.00 xxxx 1102 ATOM 1103 NE2 GLN A 141 17.405 −3.866 66.395 1.00 0.00 xxxx 1103 ATOM 1104 N TYR A 142 19.048 0.886 70.324 1.00 0.00 xxxx 1104 ATOM 1105 CA TYR A 142 19.253 1.886 71.361 1.00 0.00 xxxx 1105 ATOM 1106 C TYR A 142 19.068 3.293 70.811 1.00 0.00 xxxx 1106 ATOM 1107 O TYR A 142 19.085 3.532 69.599 1.00 0.00 xxxx 1107 ATOM 1108 CB TYR A 142 20.644 1.775 71.996 1.00 0.00 xxxx 1108 ATOM 1109 CG TYR A 142 21.784 2.201 71.095 1.00 0.00 xxxx 1109 ATOM 1110 CD1 TYR A 142 22.257 3.508 71.115 1.00 0.00 xxxx 1110 ATOM 1111 CD2 TYR A 142 22.402 1.298 70.239 1.00 0.00 xxxx 1111 ATOM 1112 CE1 TYR A 142 23.303 3.906 70.304 1.00 0.00 xxxx 1112 ATOM 1113 CE2 TYR A 142 23.450 1.681 69.428 1.00 0.00 xxxx 1113 ATOM 1114 CZ TYR A 142 23.894 2.990 69.456 1.00 0.00 xxxx 1114 ATOM 1115 OH TYR A 142 24.936 3.386 68.661 1.00 0.00 xxxx 1115 ATOM 1116 N VAL A 143 18.883 4.230 71.738 1.00 0.00 xxxx 1116 ATOM 1117 CA VAL A 143 18.962 5.652 71.435 1.00 0.00 xxxx 1117 ATOM 1118 C VAL A 143 20.031 6.273 72.337 1.00 0.00 xxxx 1118 ATOM 1119 O VAL A 143 20.359 5.757 73.414 1.00 0.00 xxxx 1119 ATOM 1120 CB VAL A 143 17.605 6.379 71.563 1.00 0.00 xxxx 1120 ATOM 1121 CG1 VAL A 143 16.575 5.795 70.582 1.00 0.00 xxxx 1121 ATOM 1122 CG2 VAL A 143 17.088 6.309 73.005 1.00 0.00 xxxx 1122 ATOM 1123 N MET A 144 20.561 7.412 71.891 1.00 0.00 xxxx 1123 ATOM 1124 CA MET A 144 21.693 8.058 72.540 1.00 0.00 xxxx 1124 ATOM 1125 C MET A 144 21.416 9.548 72.683 1.00 0.00 xxxx 1125 ATOM 1126 O MET A 144 21.234 10.247 71.675 1.00 0.00 xxxx 1126 ATOM 1127 CB MET A 144 22.955 7.829 71.701 1.00 0.00 xxxx 1127 ATOM 1128 CG MET A 144 24.158 8.670 72.136 1.00 0.00 xxxx 1128 ATOM 1129 SD MET A 144 24.866 8.211 73.720 1.00 0.00 xxxx 1129 ATOM 1130 CE MET A 144 25.631 6.652 73.300 1.00 0.00 xxxx 1130 ATOM 1131 N LEU A 145 21.407 10.030 73.924 1.00 0.00 xxxx 1131 ATOM 1132 CA LEU A 145 21.252 11.456 74.226 1.00 0.00 xxxx 1132 ATOM 1133 C LEU A 145 22.628 12.034 74.512 1.00 0.00 xxxx 1133 ATOM 1134 O LEU A 145 23.225 11.765 75.565 1.00 0.00 xxxx 1134 ATOM 1135 CB LEU A 145 20.324 11.660 75.424 1.00 0.00 xxxx 1135 ATOM 1136 CG LEU A 145 18.866 11.314 75.142 1.00 0.00 xxxx 1136 ATOM 1137 CD1 LEU A 145 18.133 10.928 76.428 1.00 0.00 xxxx 1137 ATOM 1138 CD2 LEU A 145 18.168 12.496 74.475 1.00 0.00 xxxx 1138 ATOM 1139 N MET A 146 23.136 12.811 73.570 1.00 0.00 xxxx 1139 ATOM 1140 CA MET A 146 24.437 13.437 73.707 1.00 0.00 xxxx 1140 ATOM 1141 C MET A 146 24.308 14.773 74.425 1.00 0.00 xxxx 1141 ATOM 1142 O MET A 146 23.244 15.412 74.435 1.00 0.00 xxxx 1142 ATOM 1143 CB MET A 146 25.059 13.655 72.327 1.00 0.00 xxxx 1143 ATOM 1144 CG MET A 146 25.250 12.362 71.514 1.00 0.00 xxxx 1144 ATOM 1145 SD MET A 146 26.103 12.630 69.952 1.00 0.00 xxxx 1145 ATOM 1146 CE MET A 146 24.844 13.565 69.077 1.00 0.00 xxxx 1146 ATOM 1147 O GLY A 147 24.826 17.862 73.869 1.00 0.00 xxxx 1147 ATOM 1148 N GLY A 147 25.415 15.202 75.022 1.00 0.00 xxxx 1148 ATOM 1149 CA GLY A 147 25.436 16.476 75.723 1.00 0.00 xxxx 1149 ATOM 1150 C GLY A 147 25.590 17.683 74.822 1.00 0.00 xxxx 1150 ATOM 1151 N GLU A 148 26.569 18.521 75.124 1.00 0.00 xxxx 1151 ATOM 1152 CA GLU A 148 26.830 19.738 74.364 1.00 0.00 xxxx 1152 ATOM 1153 C GLU A 148 27.800 19.435 73.230 1.00 0.00 xxxx 1153 ATOM 1154 O GLU A 148 28.843 18.813 73.472 1.00 0.00 xxxx 1154 ATOM 1155 CB GLU A 148 27.474 20.786 75.259 1.00 0.00 xxxx 1155 ATOM 1156 CG GLU A 148 26.577 21.408 76.319 1.00 0.00 xxxx 1156 ATOM 1157 CD GLU A 148 27.303 22.486 77.115 1.00 0.00 xxxx 1157 ATOM 1158 OE1 GLU A 148 28.551 22.430 77.195 1.00 0.00 xxxx 1158 ATOM 1159 OE2 GLU A 148 26.631 23.394 77.651 1.00 0.00 xxxx 1159 ATOM 1160 N PRO A 149 27.507 19.872 72.005 1.00 0.00 xxxx 1160 ATOM 1161 CA PRO A 149 28.435 19.633 70.884 1.00 0.00 xxxx 1161 ATOM 1162 C PRO A 149 29.837 20.134 71.206 1.00 0.00 xxxx 1162 ATOM 1163 O PRO A 149 30.029 21.262 71.667 1.00 0.00 xxxx 1163 ATOM 1164 CB PRO A 149 27.817 20.432 69.728 1.00 0.00 xxxx 1164 ATOM 1165 CG PRO A 149 26.358 20.518 70.061 1.00 0.00 xxxx 1165 ATOM 1166 CD PRO A 149 26.263 20.535 71.571 1.00 0.00 xxxx 1166 ATOM 1167 N GLY A 150 30.819 19.267 71.005 1.00 0.00 xxxx 1167 ATOM 1168 CA GLY A 150 32.191 19.679 71.219 1.00 0.00 xxxx 1168 ATOM 1169 C GLY A 150 32.672 19.657 72.657 1.00 0.00 xxxx 1169 ATOM 1170 O GLY A 150 33.853 19.917 72.892 1.00 0.00 xxxx 1170 ATOM 1171 N HIS A 151 31.811 19.374 73.627 1.00 0.00 xxxx 1171 ATOM 1172 CA HIS A 151 32.271 19.161 74.993 1.00 0.00 xxxx 1172 ATOM 1173 C HIS A 151 33.023 17.836 75.007 1.00 0.00 xxxx 1173 ATOM 1174 O HIS A 151 32.548 16.854 74.436 1.00 0.00 xxxx 1174 ATOM 1175 CB HIS A 151 31.026 19.066 75.879 1.00 0.00 xxxx 1175 ATOM 1176 CG HIS A 151 31.279 19.122 77.355 1.00 0.00 xxxx 1176 ATOM 1177 ND1 HIS A 151 32.075 18.215 78.024 1.00 0.00 xxxx 1177 ATOM 1178 CD2 HIS A 151 30.743 19.927 78.305 1.00 0.00 xxxx 1178 ATOM 1179 CE1 HIS A 151 32.060 18.497 79.320 1.00 0.00 xxxx 1179 ATOM 1180 NE2 HIS A 151 31.259 19.530 79.516 1.00 0.00 xxxx 1180 ATOM 1181 N GLN A 152 34.205 17.798 75.636 1.00 0.00 xxxx 1181 ATOM 1182 CA GLN A 152 34.984 16.565 75.564 1.00 0.00 xxxx 1182 ATOM 1183 C GLN A 152 34.239 15.390 76.189 1.00 0.00 xxxx 1183 ATOM 1184 O GLN A 152 34.395 14.242 75.743 1.00 0.00 xxxx 1184 ATOM 1185 CB GLN A 152 36.365 16.753 76.199 1.00 0.00 xxxx 1185 ATOM 1186 CG GLN A 152 36.399 16.645 77.736 1.00 0.00 xxxx 1186 ATOM 1187 CD GLN A 152 35.868 17.885 78.446 1.00 0.00 xxxx 1187 ATOM 1188 OE1 GLN A 152 35.823 18.983 77.878 1.00 0.00 xxxx 1188 ATOM 1189 NE2 GLN A 152 35.489 17.713 79.712 1.00 0.00 xxxx 1189 ATOM 1190 N ASP A 153 33.406 15.643 77.203 1.00 0.00 xxxx 1190 ATOM 1191 CA ASP A 153 32.689 14.532 77.822 1.00 0.00 xxxx 1191 ATOM 1192 C ASP A 153 31.615 13.986 76.890 1.00 0.00 xxxx 1192 ATOM 1193 O ASP A 153 31.383 12.771 76.853 1.00 0.00 xxxx 1193 ATOM 1194 CB ASP A 153 32.064 14.961 79.148 1.00 0.00 xxxx 1194 ATOM 1195 CG ASP A 153 33.095 15.277 80.215 1.00 0.00 xxxx 1195 ATOM 1196 OD1 ASP A 153 34.296 14.931 80.061 1.00 0.00 xxxx 1196 ATOM 1197 OD2 ASP A 153 32.701 15.876 81.232 1.00 0.00 xxxx 1197 ATOM 1198 N ALA A 154 30.964 14.862 76.115 1.00 0.00 xxxx 1198 ATOM 1199 CA ALA A 154 29.979 14.370 75.161 1.00 0.00 xxxx 1199 ATOM 1200 C ALA A 154 30.644 13.545 74.074 1.00 0.00 xxxx 1200 ATOM 1201 O ALA A 154 30.166 12.455 73.733 1.00 0.00 xxxx 1201 ATOM 1202 CB ALA A 154 29.177 15.525 74.558 1.00 0.00 xxxx 1202 ATOM 1203 N ILE A 155 31.762 14.032 73.542 1.00 0.00 xxxx 1203 ATOM 1204 CA ILE A 155 32.466 13.305 72.491 1.00 0.00 xxxx 1204 ATOM 1205 C ILE A 155 32.849 11.911 72.974 1.00 0.00 xxxx 1205 ATOM 1206 O ILE A 155 32.526 10.898 72.339 1.00 0.00 xxxx 1206 ATOM 1207 CB ILE A 155 33.694 14.109 72.028 1.00 0.00 xxxx 1207 ATOM 1208 CG1 ILE A 155 33.273 15.433 71.375 1.00 0.00 xxxx 1208 ATOM 1209 CG2 ILE A 155 34.527 13.289 71.054 1.00 0.00 xxxx 1209 ATOM 1210 CD1 ILE A 155 34.421 16.397 71.165 1.00 0.00 xxxx 1210 ATOM 1211 N LEU A 156 33.498 11.835 74.134 1.00 0.00 xxxx 1211 ATOM 1212 CA LEU A 156 34.123 10.585 74.552 1.00 0.00 xxxx 1212 ATOM 1213 C LEU A 156 33.131 9.618 75.197 1.00 0.00 xxxx 1213 ATOM 1214 O LEU A 156 33.229 8.403 74.991 1.00 0.00 xxxx 1214 ATOM 1215 CB LEU A 156 35.308 10.892 75.465 1.00 0.00 xxxx 1215 ATOM 1216 CG LEU A 156 36.440 11.611 74.728 1.00 0.00 xxxx 1216 ATOM 1217 CD1 LEU A 156 37.439 12.150 75.743 1.00 0.00 xxxx 1217 ATOM 1218 CD2 LEU A 156 37.134 10.715 73.700 1.00 0.00 xxxx 1218 ATOM 1219 N ARG A 157 32.159 10.119 75.961 1.00 0.00 xxxx 1219 ATOM 1220 CA ARG A 157 31.169 9.206 76.539 1.00 0.00 xxxx 1220 ATOM 1221 C ARG A 157 30.329 8.554 75.453 1.00 0.00 xxxx 1221 ATOM 1222 O ARG A 157 29.998 7.367 75.547 1.00 0.00 xxxx 1222 ATOM 1223 CB ARG A 157 30.271 9.934 77.538 1.00 0.00 xxxx 1223 ATOM 1224 CG ARG A 157 30.988 10.314 78.814 1.00 0.00 xxxx 1224 ATOM 1225 CD ARG A 157 30.118 11.204 79.671 1.00 0.00 xxxx 1225 ATOM 1226 NE ARG A 157 30.846 11.651 80.851 1.00 0.00 xxxx 1226 ATOM 1227 CZ ARG A 157 30.435 12.638 81.635 1.00 0.00 xxxx 1227 ATOM 1228 NH1 ARG A 157 29.287 13.248 81.365 1.00 0.00 xxxx 1228 ATOM 1229 NH2 ARG A 157 31.153 13.017 82.682 1.00 0.00 xxxx 1229 ATOM 1230 N THR A 158 29.976 9.320 74.421 1.00 0.00 xxxx 1230 ATOM 1231 CA THR A 158 29.191 8.785 73.315 1.00 0.00 xxxx 1231 ATOM 1232 C THR A 158 29.959 7.686 72.595 1.00 0.00 xxxx 1232 ATOM 1233 O THR A 158 29.416 6.605 72.330 1.00 0.00 xxxx 1233 ATOM 1234 CB THR A 158 28.833 9.930 72.372 1.00 0.00 xxxx 1234 ATOM 1235 OG1 THR A 158 28.018 10.882 73.082 1.00 0.00 xxxx 1235 ATOM 1236 CG2 THR A 158 28.062 9.415 71.167 1.00 0.00 xxxx 1236 ATOM 1237 N GLN A 159 31.233 7.940 72.272 1.00 0.00 xxxx 1237 ATOM 1238 CA GLN A 159 32.036 6.955 71.558 1.00 0.00 xxxx 1238 ATOM 1239 C GLN A 159 32.249 5.703 72.401 1.00 0.00 xxxx 1239 ATOM 1240 O GLN A 159 31.998 4.580 71.945 1.00 0.00 xxxx 1240 ATOM 1241 CB GLN A 159 33.383 7.574 71.176 1.00 0.00 xxxx 1241 ATOM 1242 CG GLN A 159 34.323 6.608 70.470 1.00 0.00 xxxx 1242 ATOM 1243 CD GLN A 159 35.726 7.162 70.282 1.00 0.00 xxxx 1243 ATOM 1244 OE1 GLN A 159 36.606 6.481 69.755 1.00 0.00 xxxx 1244 ATOM 1245 NE2 GLN A 159 35.940 8.397 70.714 1.00 0.00 xxxx 1245 ATOM 1246 N TYR A 160 32.726 5.877 73.632 1.00 0.00 xxxx 1246 ATOM 1247 CA TYR A 160 33.216 4.739 74.401 1.00 0.00 xxxx 1247 ATOM 1248 C TYR A 160 32.105 3.875 74.979 1.00 0.00 xxxx 1248 ATOM 1249 O TYR A 160 32.308 2.669 75.158 1.00 0.00 xxxx 1249 ATOM 1250 CB TYR A 160 34.204 5.198 75.472 1.00 0.00 xxxx 1250 ATOM 1251 CG TYR A 160 35.601 5.391 74.914 1.00 0.00 xxxx 1251 ATOM 1252 CD1 TYR A 160 35.946 6.552 74.224 1.00 0.00 xxxx 1252 ATOM 1253 CD2 TYR A 160 36.569 4.399 75.043 1.00 0.00 xxxx 1253 ATOM 1254 CE1 TYR A 160 37.221 6.732 73.701 1.00 0.00 xxxx 1254 ATOM 1255 CE2 TYR A 160 37.844 4.572 74.517 1.00 0.00 xxxx 1255 ATOM 1256 CZ TYR A 160 38.156 5.739 73.849 1.00 0.00 xxxx 1256 ATOM 1257 OH TYR A 160 39.427 5.902 73.335 1.00 0.00 xxxx 1257 ATOM 1258 N SER A 161 30.942 4.453 75.289 1.00 0.00 xxxx 1258 ATOM 1259 CA SER A 161 29.842 3.626 75.783 1.00 0.00 xxxx 1259 ATOM 1260 C SER A 161 29.450 2.579 74.750 1.00 0.00 xxxx 1260 ATOM 1261 O SER A 161 29.409 1.380 75.045 1.00 0.00 xxxx 1261 ATOM 1262 CB SER A 161 28.635 4.486 76.172 1.00 0.00 xxxx 1262 ATOM 1263 OG SER A 161 28.180 5.293 75.088 1.00 0.00 xxxx 1263 ATOM 1264 N ILE A 162 29.211 3.013 73.512 1.00 0.00 xxxx 1264 ATOM 1265 CA ILE A 162 28.751 2.089 72.486 1.00 0.00 xxxx 1265 ATOM 1266 C ILE A 162 29.858 1.119 72.084 1.00 0.00 xxxx 1266 ATOM 1267 O ILE A 162 29.612 −0.081 71.896 1.00 0.00 xxxx 1267 ATOM 1268 CB ILE A 162 28.164 2.856 71.291 1.00 0.00 xxxx 1268 ATOM 1269 CG1 ILE A 162 26.955 3.692 71.732 1.00 0.00 xxxx 1269 ATOM 1270 CG2 ILE A 162 27.772 1.878 70.193 1.00 0.00 xxxx 1270 ATOM 1271 CD1 ILE A 162 25.902 2.898 72.512 1.00 0.00 xxxx 1271 ATOM 1272 N GLN A 163 31.097 1.609 71.946 1.00 0.00 xxxx 1272 ATOM 1273 CA GLN A 163 32.182 0.701 71.592 1.00 0.00 xxxx 1273 ATOM 1274 C GLN A 163 32.360 −0.382 72.651 1.00 0.00 xxxx 1274 ATOM 1275 O GLN A 163 32.675 −1.531 72.318 1.00 0.00 xxxx 1275 ATOM 1276 CB GLN A 163 33.485 1.469 71.379 1.00 0.00 xxxx 1276 ATOM 1277 CG GLN A 163 34.589 0.592 70.798 1.00 0.00 xxxx 1277 ATOM 1278 CD GLN A 163 34.210 0.021 69.443 1.00 0.00 xxxx 1278 ATOM 1279 OE1 GLN A 163 33.819 0.760 68.534 1.00 0.00 xxxx 1279 ATOM 1280 NE2 GLN A 163 34.325 −1.297 69.299 1.00 0.00 xxxx 1280 ATOM 1281 N THR A 164 32.138 −0.042 73.924 1.00 0.00 xxxx 1281 ATOM 1282 CA THR A 164 32.266 −1.035 74.989 1.00 0.00 xxxx 1282 ATOM 1283 C THR A 164 31.188 −2.114 74.887 1.00 0.00 xxxx 1283 ATOM 1284 O THR A 164 31.462 −3.298 75.115 1.00 0.00 xxxx 1284 ATOM 1285 CB THR A 164 32.231 −0.326 76.339 1.00 0.00 xxxx 1285 ATOM 1286 OG1 THR A 164 33.385 0.516 76.443 1.00 0.00 xxxx 1286 ATOM 1287 CG2 THR A 164 32.192 −1.322 77.498 1.00 0.00 xxxx 1287 ATOM 1288 N VAL A 165 29.962 −1.726 74.523 1.00 0.00 xxxx 1288 ATOM 1289 CA VAL A 165 28.908 −2.715 74.291 1.00 0.00 xxxx 1289 ATOM 1290 C VAL A 165 29.292 −3.652 73.148 1.00 0.00 xxxx 1290 ATOM 1291 O VAL A 165 29.170 −4.881 73.256 1.00 0.00 xxxx 1291 ATOM 1292 CB VAL A 165 27.558 −2.016 74.045 1.00 0.00 xxxx 1292 ATOM 1293 CG1 VAL A 165 26.507 −3.043 73.702 1.00 0.00 xxxx 1293 ATOM 1294 CG2 VAL A 165 27.136 −1.217 75.278 1.00 0.00 xxxx 1294 ATOM 1295 N LYS A 166 29.769 −3.081 72.031 1.00 0.00 xxxx 1295 ATOM 1296 CA LYS A 166 30.209 −3.908 70.910 1.00 0.00 xxxx 1296 ATOM 1297 C LYS A 166 31.347 −4.835 71.321 1.00 0.00 xxxx 1297 ATOM 1298 O LYS A 166 31.358 −6.019 70.956 1.00 0.00 xxxx 1298 ATOM 1299 CB LYS A 166 30.642 −3.042 69.724 1.00 0.00 xxxx 1299 ATOM 1300 CG LYS A 166 29.518 −2.242 69.057 1.00 0.00 xxxx 1300 ATOM 1301 CD LYS A 166 30.103 −1.408 67.921 1.00 0.00 xxxx 1301 ATOM 1302 CE LYS A 166 29.086 −0.449 67.330 1.00 0.00 xxxx 1302 ATOM 1303 NZ LYS A 166 29.719 0.434 66.305 1.00 0.00 xxxx 1303 ATOM 1304 N ASP A 167 32.314 −4.317 72.091 1.00 0.00 xxxx 1304 ATOM 1305 CA ASP A 167 33.450 −5.133 72.516 1.00 0.00 xxxx 1305 ATOM 1306 C ASP A 167 33.025 −6.249 73.457 1.00 0.00 xxxx 1306 ATOM 1307 O ASP A 167 33.751 −7.243 73.593 1.00 0.00 xxxx 1307 ATOM 1308 CB ASP A 167 34.501 −4.266 73.205 1.00 0.00 xxxx 1308 ATOM 1309 CG ASP A 167 35.185 −3.296 72.251 1.00 0.00 xxxx 1309 ATOM 1310 OD1 ASP A 167 35.057 −3.472 71.021 1.00 0.00 xxxx 1310 ATOM 1311 OD2 ASP A 167 35.853 −2.359 72.741 1.00 0.00 xxxx 1311 ATOM 1312 N ALA A 168 31.877 −6.097 74.113 1.00 0.00 xxxx 1312 ATOM 1313 CA ALA A 168 31.300 −7.137 74.956 1.00 0.00 xxxx 1313 ATOM 1314 C ALA A 168 30.633 −8.245 74.151 1.00 0.00 xxxx 1314 ATOM 1315 O ALA A 168 30.095 −9.183 74.748 1.00 0.00 xxxx 1315 ATOM 1316 CB ALA A 168 30.296 −6.524 75.940 1.00 0.00 xxxx 1316 ATOM 1317 N GLY A 169 30.670 −8.168 72.823 1.00 0.00 xxxx 1317 ATOM 1318 CA GLY A 169 30.091 −9.188 71.970 1.00 0.00 xxxx 1318 ATOM 1319 C GLY A 169 28.645 −8.970 71.596 1.00 0.00 xxxx 1319 ATOM 1320 O GLY A 169 28.017 −9.884 71.050 1.00 0.00 xxxx 1320 ATOM 1321 N ILE A 170 28.099 −7.792 71.854 1.00 0.00 xxxx 1321 ATOM 1322 CA ILE A 170 26.694 −7.506 71.609 1.00 0.00 xxxx 1322 ATOM 1323 C ILE A 170 26.583 −6.703 70.322 1.00 0.00 xxxx 1323 ATOM 1324 O ILE A 170 27.296 −5.707 70.139 1.00 0.00 xxxx 1324 ATOM 1325 CB ILE A 170 26.093 −6.735 72.795 1.00 0.00 xxxx 1325 ATOM 1326 CG1 ILE A 170 26.183 −7.579 74.066 1.00 0.00 xxxx 1326 ATOM 1327 CG2 ILE A 170 24.659 −6.295 72.475 1.00 0.00 xxxx 1327 ATOM 1328 CD1 ILE A 170 26.067 −6.777 75.344 1.00 0.00 xxxx 1328 ATOM 1329 N LYS A 171 25.697 −7.136 69.425 1.00 0.00 xxxx 1329 ATOM 1330 CA LYS A 171 25.391 −6.374 68.220 1.00 0.00 xxxx 1330 ATOM 1331 C LYS A 171 24.407 −5.264 68.570 1.00 0.00 xxxx 1331 ATOM 1332 O LYS A 171 23.503 −5.464 69.384 1.00 0.00 xxxx 1332 ATOM 1333 CB LYS A 171 24.764 −7.289 67.167 1.00 0.00 xxxx 1333 ATOM 1334 CG LYS A 171 25.686 −8.416 66.699 1.00 0.00 xxxx 1334 ATOM 1335 CD LYS A 171 24.971 −9.366 65.729 1.00 0.00 xxxx 1335 ATOM 1336 CE LYS A 171 25.825 −10.588 65.435 1.00 0.00 xxxx 1336 ATOM 1337 NZ LYS A 171 25.031 −11.698 64.837 1.00 0.00 xxxx 1337 ATOM 1338 N VAL A 172 24.593 −4.083 67.966 1.00 0.00 xxxx 1338 ATOM 1339 CA VAL A 172 23.787 −2.912 68.297 1.00 0.00 xxxx 1339 ATOM 1340 C VAL A 172 23.218 −2.271 67.036 1.00 0.00 xxxx 1340 ATOM 1341 O VAL A 172 23.733 −2.440 65.927 1.00 0.00 xxxx 1341 ATOM 1342 CB VAL A 172 24.574 −1.866 69.114 1.00 0.00 xxxx 1342 ATOM 1343 CG1 VAL A 172 25.130 −2.494 70.391 1.00 0.00 xxxx 1343 ATOM 1344 CG2 VAL A 172 25.686 −1.255 68.279 1.00 0.00 xxxx 1344 ATOM 1345 N GLN A 173 22.145 −1.498 67.226 1.00 0.00 xxxx 1345 ATOM 1346 CA GLN A 173 21.547 −0.710 66.155 1.00 0.00 xxxx 1346 ATOM 1347 C GLN A 173 21.113 0.620 66.741 1.00 0.00 xxxx 1347 ATOM 1348 O GLN A 173 20.268 0.654 67.635 1.00 0.00 xxxx 1348 ATOM 1349 CB GLN A 173 20.343 −1.417 65.536 1.00 0.00 xxxx 1349 ATOM 1350 CG GLN A 173 19.716 −0.603 64.411 1.00 0.00 xxxx 1350 ATOM 1351 CD GLN A 173 18.550 −1.322 63.755 1.00 0.00 xxxx 1351 ATOM 1352 OE1 GLN A 173 17.694 −1.888 64.437 1.00 0.00 xxxx 1352 ATOM 1353 NE2 GLN A 173 18.504 −1.298 62.422 1.00 0.00 xxxx 1353 ATOM 1354 N GLU A 174 21.667 1.708 66.216 1.00 0.00 xxxx 1354 ATOM 1355 CA GLU A 174 21.374 3.052 66.698 1.00 0.00 xxxx 1355 ATOM 1356 C GLU A 174 20.115 3.563 66.003 1.00 0.00 xxxx 1356 ATOM 1357 O GLU A 174 20.152 3.932 64.825 1.00 0.00 xxxx 1357 ATOM 1358 CB GLU A 174 22.555 3.952 66.369 1.00 0.00 xxxx 1358 ATOM 1359 CG GLU A 174 22.459 5.336 66.957 1.00 0.00 xxxx 1359 ATOM 1360 CD GLU A 174 23.746 6.107 66.755 1.00 0.00 xxxx 1360 ATOM 1361 OE1 GLU A 174 23.782 6.964 65.861 1.00 0.00 xxxx 1361 ATOM 1362 OE2 GLU A 174 24.724 5.832 67.487 1.00 0.00 xxxx 1362 ATOM 1363 N LEU A 175 19.000 3.589 66.736 1.00 0.00 xxxx 1363 ATOM 1364 CA LEU A 175 17.750 4.086 66.168 1.00 0.00 xxxx 1364 ATOM 1365 C LEU A 175 17.743 5.599 66.073 1.00 0.00 xxxx 1365 ATOM 1366 O LEU A 175 17.143 6.155 65.145 1.00 0.00 xxxx 1366 ATOM 1367 CB LEU A 175 16.565 3.645 67.029 1.00 0.00 xxxx 1367 ATOM 1368 CG LEU A 175 16.264 2.145 67.095 1.00 0.00 xxxx 1368 ATOM 1369 CD1 LEU A 175 15.106 1.900 68.076 1.00 0.00 xxxx 1369 ATOM 1370 CD2 LEU A 175 15.921 1.605 65.723 1.00 0.00 xxxx 1370 ATOM 1371 N ALA A 176 18.385 6.272 67.022 1.00 0.00 xxxx 1371 ATOM 1372 CA ALA A 176 18.405 7.726 67.039 1.00 0.00 xxxx 1372 ATOM 1373 C ALA A 176 19.520 8.206 67.955 1.00 0.00 xxxx 1373 ATOM 1374 O ALA A 176 19.854 7.567 68.956 1.00 0.00 xxxx 1374 ATOM 1375 CB ALA A 176 17.061 8.289 67.522 1.00 0.00 xxxx 1375 ATOM 1376 N LYS A 177 20.073 9.361 67.610 1.00 0.00 xxxx 1376 ATOM 1377 CA LYS A 177 21.068 10.012 68.447 1.00 0.00 xxxx 1377 ATOM 1378 C LYS A 177 20.969 11.508 68.191 1.00 0.00 xxxx 1378 ATOM 1379 O LYS A 177 20.868 11.934 67.036 1.00 0.00 xxxx 1379 ATOM 1380 CB LYS A 177 22.451 9.486 68.063 1.00 0.00 xxxx 1380 ATOM 1381 CG LYS A 177 23.620 10.280 68.569 1.00 0.00 xxxx 1381 ATOM 1382 CD LYS A 177 24.936 9.671 68.080 1.00 0.00 xxxx 1382 ATOM 1383 CE LYS A 177 25.116 9.859 66.580 1.00 0.00 xxxx 1383 ATOM 1384 NZ LYS A 177 26.421 9.325 66.103 1.00 0.00 xxxx 1384 ATOM 1385 N ASP A 178 20.972 12.305 69.256 1.00 0.00 xxxx 1385 ATOM 1386 CA ASP A 178 20.891 13.751 69.083 1.00 0.00 xxxx 1386 ATOM 1387 C ASP A 178 21.464 14.426 70.321 1.00 0.00 xxxx 1387 ATOM 1388 O ASP A 178 21.598 13.806 71.386 1.00 0.00 xxxx 1388 ATOM 1389 CB ASP A 178 19.438 14.192 68.859 1.00 0.00 xxxx 1389 ATOM 1390 CG ASP A 178 19.325 15.526 68.130 1.00 0.00 xxxx 1390 ATOM 1391 OD1 ASP A 178 20.358 16.190 67.860 1.00 0.00 xxxx 1391 ATOM 1392 OD2 ASP A 178 18.171 15.921 67.840 1.00 0.00 xxxx 1392 ATOM 1393 N TYR A 179 21.795 15.709 70.170 1.00 0.00 xxxx 1393 ATOM 1394 CA TYR A 179 22.231 16.525 71.294 1.00 0.00 xxxx 1394 ATOM 1395 C TYR A 179 21.036 17.016 72.102 1.00 0.00 xxxx 1395 ATOM 1396 O TYR A 179 20.065 17.544 71.543 1.00 0.00 xxxx 1396 ATOM 1397 CB TYR A 179 22.997 17.731 70.768 1.00 0.00 xxxx 1397 ATOM 1398 CG TYR A 179 24.266 17.368 70.052 1.00 0.00 xxxx 1398 ATOM 1399 CD1 TYR A 179 25.388 16.951 70.763 1.00 0.00 xxxx 1399 ATOM 1400 CD2 TYR A 179 24.364 17.476 68.668 1.00 0.00 xxxx 1400 ATOM 1401 CE1 TYR A 179 26.562 16.628 70.123 1.00 0.00 xxxx 1401 ATOM 1402 CE2 TYR A 179 25.540 17.153 68.015 1.00 0.00 xxxx 1402 ATOM 1403 CZ TYR A 179 26.634 16.732 68.753 1.00 0.00 xxxx 1403 ATOM 1404 OH TYR A 179 27.818 16.416 68.129 1.00 0.00 xxxx 1404 ATOM 1405 N ALA A 180 21.129 16.886 73.425 1.00 0.00 xxxx 1405 ATOM 1406 CA ALA A 180 20.161 17.491 74.341 1.00 0.00 xxxx 1406 ATOM 1407 C ALA A 180 20.827 18.427 75.349 1.00 0.00 xxxx 1407 ATOM 1408 O ALA A 180 20.185 18.846 76.324 1.00 0.00 xxxx 1408 ATOM 1409 CB ALA A 180 19.282 16.432 75.019 1.00 0.00 xxxx 1409 ATOM 1410 N ASN A 181 22.103 18.760 75.148 1.00 0.00 xxxx 1410 ATOM 1411 CA ASN A 181 22.741 19.891 75.828 1.00 0.00 xxxx 1411 ATOM 1412 C ASN A 181 22.737 19.750 77.348 1.00 0.00 xxxx 1412 ATOM 1413 O ASN A 181 22.585 20.733 78.075 1.00 0.00 xxxx 1413 ATOM 1414 CB ASN A 181 22.109 21.218 75.410 1.00 0.00 xxxx 1414 ATOM 1415 CG ASN A 181 22.101 21.407 73.914 1.00 0.00 xxxx 1415 ATOM 1416 OD1 ASN A 181 23.098 21.152 73.242 1.00 0.00 xxxx 1416 ATOM 1417 ND2 ASN A 181 20.967 21.841 73.379 1.00 0.00 xxxx 1417 ATOM 1418 N CYS A 182 22.892 18.522 77.836 1.00 0.00 xxxx 1418 ATOM 1419 CA CYS A 182 23.033 18.226 79.262 1.00 0.00 xxxx 1419 ATOM 1420 C CYS A 182 21.808 18.592 80.072 1.00 0.00 xxxx 1420 ATOM 1421 O CYS A 182 21.891 18.631 81.308 1.00 0.00 xxxx 1421 ATOM 1422 CB CYS A 182 24.251 18.909 79.885 1.00 0.00 xxxx 1422 ATOM 1423 SG CYS A 182 25.697 18.733 78.864 1.00 0.00 xxxx 1423 ATOM 1424 N ASP A 183 20.679 18.850 79.417 1.00 0.00 xxxx 1424 ATOM 1425 CA ASP A 183 19.525 19.500 80.025 1.00 0.00 xxxx 1425 ATOM 1426 C ASP A 183 18.357 18.525 80.123 1.00 0.00 xxxx 1426 ATOM 1427 O ASP A 183 18.018 17.854 79.145 1.00 0.00 xxxx 1427 ATOM 1428 CB ASP A 183 19.134 20.721 79.186 1.00 0.00 xxxx 1428 ATOM 1429 CG ASP A 183 17.898 21.418 79.700 1.00 0.00 xxxx 1429 ATOM 1430 OD1 ASP A 183 17.964 22.029 80.787 1.00 0.00 xxxx 1430 ATOM 1431 OD2 ASP A 183 16.865 21.371 79.002 1.00 0.00 xxxx 1431 ATOM 1432 N ARG A 184 17.722 18.489 81.299 1.00 0.00 xxxx 1432 ATOM 1433 CA ARG A 184 16.621 17.559 81.545 1.00 0.00 xxxx 1433 ATOM 1434 C ARG A 184 15.435 17.809 80.611 1.00 0.00 xxxx 1434 ATOM 1435 O ARG A 184 14.903 16.872 80.007 1.00 0.00 xxxx 1435 ATOM 1436 CB ARG A 184 16.204 17.645 83.015 1.00 0.00 xxxx 1436 ATOM 1437 CG ARG A 184 15.048 16.728 83.405 1.00 0.00 xxxx 1437 ATOM 1438 CD ARG A 184 14.741 16.814 84.892 1.00 0.00 xxxx 1438 ATOM 1439 NE ARG A 184 14.478 18.190 85.306 1.00 0.00 xxxx 1439 ATOM 1440 CZ ARG A 184 13.315 18.812 85.142 1.00 0.00 xxxx 1440 ATOM 1441 NH1 ARG A 184 12.298 18.184 84.566 1.00 0.00 xxxx 1441 ATOM 1442 NH2 ARG A 184 13.168 20.067 85.551 1.00 0.00 xxxx 1442 ATOM 1443 N VAL A 185 15.000 19.066 80.470 1.00 0.00 xxxx 1443 ATOM 1444 CA VAL A 185 13.800 19.336 79.668 1.00 0.00 xxxx 1444 ATOM 1445 C VAL A 185 14.028 19.039 78.183 1.00 0.00 xxxx 1445 ATOM 1446 O VAL A 185 13.175 18.443 77.516 1.00 0.00 xxxx 1446 ATOM 1447 CB VAL A 185 13.286 20.764 79.905 1.00 0.00 xxxx 1447 ATOM 1448 CG1 VAL A 185 12.201 21.110 78.884 1.00 0.00 xxxx 1448 ATOM 1449 CG2 VAL A 185 12.752 20.892 81.327 1.00 0.00 xxxx 1449 ATOM 1450 N THR A 186 15.168 19.461 77.633 1.00 0.00 xxxx 1450 ATOM 1451 CA THR A 186 15.460 19.147 76.237 1.00 0.00 xxxx 1451 ATOM 1452 C THR A 186 15.495 17.640 76.014 1.00 0.00 xxxx 1452 ATOM 1453 O THR A 186 14.978 17.136 75.006 1.00 0.00 xxxx 1453 ATOM 1454 CB THR A 186 16.810 19.741 75.852 1.00 0.00 xxxx 1454 ATOM 1455 OG1 THR A 186 16.814 21.143 76.153 1.00 0.00 xxxx 1455 ATOM 1456 CG2 THR A 186 17.068 19.526 74.365 1.00 0.00 xxxx 1456 ATOM 1457 N ALA A 187 16.116 16.907 76.937 1.00 0.00 xxxx 1457 ATOM 1458 CA ALA A 187 16.173 15.456 76.812 1.00 0.00 xxxx 1458 ATOM 1459 C ALA A 187 14.783 14.846 76.878 1.00 0.00 xxxx 1459 ATOM 1460 O ALA A 187 14.469 13.918 76.122 1.00 0.00 xxxx 1460 ATOM 1461 CB ALA A 187 17.059 14.868 77.909 1.00 0.00 xxxx 1461 ATOM 1462 N HIS A 188 13.941 15.351 77.785 1.00 0.00 xxxx 1462 ATOM 1463 CA HIS A 188 12.551 14.900 77.834 1.00 0.00 xxxx 1463 ATOM 1464 C HIS A 188 11.883 15.050 76.474 1.00 0.00 xxxx 1464 ATOM 1465 O HIS A 188 11.220 14.127 75.989 1.00 0.00 xxxx 1465 ATOM 1466 CB HIS A 188 11.780 15.697 78.885 1.00 0.00 xxxx 1466 ATOM 1467 CG HIS A 188 10.299 15.513 78.787 1.00 0.00 xxxx 1467 ATOM 1468 ND1 HIS A 188 9.512 16.277 77.951 1.00 0.00 xxxx 1468 ATOM 1469 CD2 HIS A 188 9.467 14.632 79.390 1.00 0.00 xxxx 1469 ATOM 1470 CE1 HIS A 188 8.252 15.887 78.063 1.00 0.00 xxxx 1470 ATOM 1471 NE2 HIS A 188 8.199 14.889 78.926 1.00 0.00 xxxx 1471 ATOM 1472 N ASP A 189 12.049 16.221 75.846 1.00 0.00 xxxx 1472 ATOM 1473 CA ASP A 189 11.368 16.487 74.584 1.00 0.00 xxxx 1473 ATOM 1474 C ASP A 189 11.903 15.599 73.467 1.00 0.00 xxxx 1474 ATOM 1475 O ASP A 189 11.126 15.099 72.645 1.00 0.00 xxxx 1475 ATOM 1476 CB ASP A 189 11.479 17.973 74.226 1.00 0.00 xxxx 1476 ATOM 1477 CG ASP A 189 10.710 18.880 75.188 1.00 0.00 xxxx 1477 ATOM 1478 OD1 ASP A 189 9.954 18.372 76.049 1.00 0.00 xxxx 1478 ATOM 1479 OD2 ASP A 189 10.857 20.117 75.077 1.00 0.00 xxxx 1479 ATOM 1480 N LYS A 190 13.223 15.368 73.429 1.00 0.00 xxxx 1480 ATOM 1481 CA LYS A 190 13.777 14.496 72.396 1.00 0.00 xxxx 1481 ATOM 1482 C LYS A 190 13.285 13.068 72.579 1.00 0.00 xxxx 1482 ATOM 1483 O LYS A 190 12.891 12.408 71.606 1.00 0.00 xxxx 1483 ATOM 1484 CB LYS A 190 15.308 14.513 72.449 1.00 0.00 xxxx 1484 ATOM 1485 CG LYS A 190 15.945 15.863 72.248 1.00 0.00 xxxx 1485 ATOM 1486 CD LYS A 190 15.977 16.260 70.788 1.00 0.00 xxxx 1486 ATOM 1487 CE LYS A 190 16.701 17.585 70.608 1.00 0.00 xxxx 1487 ATOM 1488 NZ LYS A 190 16.722 17.978 69.176 1.00 0.00 xxxx 1488 ATOM 1489 N MET A 191 13.301 12.577 73.824 1.00 0.00 xxxx 1489 ATOM 1490 CA MET A 191 12.870 11.208 74.093 1.00 0.00 xxxx 1490 ATOM 1491 C MET A 191 11.392 11.025 73.776 1.00 0.00 xxxx 1491 ATOM 1492 O MET A 191 10.990 9.992 73.224 1.00 0.00 xxxx 1492 ATOM 1493 CB MET A 191 13.165 10.842 75.548 1.00 0.00 xxxx 1493 ATOM 1494 CG MET A 191 12.888 9.385 75.898 1.00 0.00 xxxx 1494 ATOM 1495 SD MET A 191 14.209 8.341 75.237 1.00 0.00 xxxx 1495 ATOM 1496 CE MET A 191 13.275 6.864 74.858 1.00 0.00 xxxx 1496 ATOM 1497 N ALA A 192 10.562 12.018 74.119 1.00 0.00 xxxx 1497 ATOM 1498 CA ALA A 192 9.135 11.911 73.822 1.00 0.00 xxxx 1498 ATOM 1499 C ALA A 192 8.894 11.783 72.320 1.00 0.00 xxxx 1499 ATOM 1500 O ALA A 192 8.039 11.002 71.882 1.00 0.00 xxxx 1500 ATOM 1501 CB ALA A 192 8.394 13.125 74.388 1.00 0.00 xxxx 1501 ATOM 1502 N ALA A 193 9.640 12.543 71.517 1.00 0.00 xxxx 1502 ATOM 1503 CA ALA A 193 9.506 12.450 70.066 1.00 0.00 xxxx 1503 ATOM 1504 C ALA A 193 9.962 11.087 69.559 1.00 0.00 xxxx 1504 ATOM 1505 O ALA A 193 9.311 10.487 68.692 1.00 0.00 xxxx 1505 ATOM 1506 CB ALA A 193 10.276 13.595 69.410 1.00 0.00 xxxx 1506 ATOM 1507 N TRP A 194 11.061 10.565 70.105 1.00 0.00 xxxx 1507 ATOM 1508 CA TRP A 194 11.526 9.246 69.692 1.00 0.00 xxxx 1508 ATOM 1509 C TRP A 194 10.520 8.165 70.052 1.00 0.00 xxxx 1509 ATOM 1510 O TRP A 194 10.333 7.207 69.293 1.00 0.00 xxxx 1510 ATOM 1511 CB TRP A 194 12.867 8.939 70.347 1.00 0.00 xxxx 1511 ATOM 1512 CG TRP A 194 14.000 9.749 69.833 1.00 0.00 xxxx 1512 ATOM 1513 CD1 TRP A 194 14.080 10.407 68.635 1.00 0.00 xxxx 1513 ATOM 1514 CD2 TRP A 194 15.233 9.977 70.505 1.00 0.00 xxxx 1514 ATOM 1515 NE1 TRP A 194 15.297 11.041 68.533 1.00 0.00 xxxx 1515 ATOM 1516 CE2 TRP A 194 16.022 10.787 69.671 1.00 0.00 xxxx 1516 ATOM 1517 CE3 TRP A 194 15.748 9.571 71.743 1.00 0.00 xxxx 1517 ATOM 1518 CZ2 TRP A 194 17.316 11.195 70.033 1.00 0.00 xxxx 1518 ATOM 1519 CZ3 TRP A 194 17.023 9.974 72.104 1.00 0.00 xxxx 1519 ATOM 1520 CH2 TRP A 194 17.791 10.779 71.250 1.00 0.00 xxxx 1520 ATOM 1521 N LEU A 195 9.876 8.283 71.217 1.00 0.00 xxxx 1521 ATOM 1522 CA LEU A 195 8.870 7.294 71.602 1.00 0.00 xxxx 1522 ATOM 1523 C LEU A 195 7.678 7.327 70.656 1.00 0.00 xxxx 1523 ATOM 1524 O LEU A 195 7.104 6.280 70.327 1.00 0.00 xxxx 1524 ATOM 1525 CB LEU A 195 8.423 7.516 73.047 1.00 0.00 xxxx 1525 ATOM 1526 CG LEU A 195 9.482 7.078 74.060 1.00 0.00 xxxx 1526 ATOM 1527 CD1 LEU A 195 9.204 7.715 75.422 1.00 0.00 xxxx 1527 ATOM 1528 CD2 LEU A 195 9.505 5.553 74.169 1.00 0.00 xxxx 1528 ATOM 1529 N SER A 196 7.294 8.521 70.208 1.00 0.00 xxxx 1529 ATOM 1530 CA SER A 196 6.212 8.625 69.237 1.00 0.00 xxxx 1530 ATOM 1531 C SER A 196 6.607 7.996 67.904 1.00 0.00 xxxx 1531 ATOM 1532 O SER A 196 5.787 7.331 67.256 1.00 0.00 xxxx 1532 ATOM 1533 CB SER A 196 5.842 10.096 69.058 1.00 0.00 xxxx 1533 ATOM 1534 OG SER A 196 4.793 10.240 68.117 1.00 0.00 xxxx 1534 ATOM 1535 N SER A 197 7.867 8.170 67.498 1.00 0.00 xxxx 1535 ATOM 1536 CA SER A 197 8.327 7.660 66.209 1.00 0.00 xxxx 1536 ATOM 1537 C SER A 197 8.543 6.155 66.227 1.00 0.00 xxxx 1537 ATOM 1538 O SER A 197 8.182 5.467 65.265 1.00 0.00 xxxx 1538 ATOM 1539 CB SER A 197 9.638 8.333 65.817 1.00 0.00 xxxx 1539 ATOM 1540 OG SER A 197 9.428 9.672 65.436 1.00 0.00 xxxx 1540 ATOM 1541 N PHE A 198 9.146 5.631 67.296 1.00 0.00 xxxx 1541 ATOM 1542 CA PHE A 198 9.667 4.272 67.310 1.00 0.00 xxxx 1542 ATOM 1543 C PHE A 198 9.012 3.374 68.341 1.00 0.00 xxxx 1543 ATOM 1544 O PHE A 198 9.050 2.147 68.178 1.00 0.00 xxxx 1544 ATOM 1545 CB PHE A 198 11.186 4.271 67.567 1.00 0.00 xxxx 1545 ATOM 1546 CG PHE A 198 11.980 5.046 66.550 1.00 0.00 xxxx 1546 ATOM 1547 CD1 PHE A 198 12.121 4.570 65.254 1.00 0.00 xxxx 1547 ATOM 1548 CD2 PHE A 198 12.595 6.237 66.891 1.00 0.00 xxxx 1548 ATOM 1549 CE1 PHE A 198 12.854 5.280 64.315 1.00 0.00 xxxx 1549 ATOM 1550 CE2 PHE A 198 13.327 6.954 65.959 1.00 0.00 xxxx 1550 ATOM 1551 CZ PHE A 198 13.459 6.474 64.672 1.00 0.00 xxxx 1551 ATOM 1552 N GLY A 199 8.436 3.938 69.396 1.00 0.00 xxxx 1552 ATOM 1553 CA GLY A 199 7.622 3.144 70.303 1.00 0.00 xxxx 1553 ATOM 1554 C GLY A 199 8.407 2.021 70.947 1.00 0.00 xxxx 1554 ATOM 1555 O GLY A 199 9.526 2.204 71.447 1.00 0.00 xxxx 1555 ATOM 1556 N ASP A 200 7.823 0.827 70.915 1.00 0.00 xxxx 1556 ATOM 1557 CA ASP A 200 8.417 −0.299 71.617 1.00 0.00 xxxx 1557 ATOM 1558 C ASP A 200 9.670 −0.829 70.935 1.00 0.00 xxxx 1558 ATOM 1559 O ASP A 200 10.269 −1.778 71.448 1.00 0.00 xxxx 1559 ATOM 1560 CB ASP A 200 7.385 −1.416 71.804 1.00 0.00 xxxx 1560 ATOM 1561 CG ASP A 200 7.738 −2.355 72.951 1.00 0.00 xxxx 1561 ATOM 1562 OD1 ASP A 200 8.129 −1.859 74.030 1.00 0.00 xxxx 1562 ATOM 1563 OD2 ASP A 200 7.629 −3.588 72.771 1.00 0.00 xxxx 1563 ATOM 1564 N LYS A 201 10.100 −0.242 69.813 1.00 0.00 xxxx 1564 ATOM 1565 CA LYS A 201 11.350 −0.688 69.204 1.00 0.00 xxxx 1565 ATOM 1566 C LYS A 201 12.558 −0.358 70.073 1.00 0.00 xxxx 1566 ATOM 1567 O LYS A 201 13.589 −1.034 69.975 1.00 0.00 xxxx 1567 ATOM 1568 CB LYS A 201 11.546 −0.053 67.826 1.00 0.00 xxxx 1568 ATOM 1569 CG LYS A 201 10.675 −0.615 66.715 1.00 0.00 xxxx 1569 ATOM 1570 CD LYS A 201 10.986 0.110 65.409 1.00 0.00 xxxx 1570 ATOM 1571 CE LYS A 201 10.412 −0.603 64.198 1.00 0.00 xxxx 1571 ATOM 1572 NZ LYS A 201 11.042 −1.941 64.005 1.00 0.00 xxxx 1572 ATOM 1573 N ILE A 202 12.474 0.683 70.904 1.00 0.00 xxxx 1573 ATOM 1574 CA ILE A 202 13.634 1.098 71.688 1.00 0.00 xxxx 1574 ATOM 1575 C ILE A 202 13.860 0.108 72.824 1.00 0.00 xxxx 1575 ATOM 1576 O ILE A 202 12.953 −0.158 73.623 1.00 0.00 xxxx 1576 ATOM 1577 CB ILE A 202 13.439 2.518 72.238 1.00 0.00 xxxx 1577 ATOM 1578 CG1 ILE A 202 13.178 3.517 71.109 1.00 0.00 xxxx 1578 ATOM 1579 CG2 ILE A 202 14.660 2.953 73.069 1.00 0.00 xxxx 1579 ATOM 1580 CD1 ILE A 202 12.815 4.917 71.597 1.00 0.00 xxxx 1580 ATOM 1581 N GLU A 203 15.077 −0.424 72.911 1.00 0.00 xxxx 1581 ATOM 1582 CA GLU A 203 15.426 −1.422 73.910 1.00 0.00 xxxx 1582 ATOM 1583 C GLU A 203 16.410 −0.926 74.962 1.00 0.00 xxxx 1583 ATOM 1584 O GLU A 203 16.580 −1.596 75.992 1.00 0.00 xxxx 1584 ATOM 1585 CB GLU A 203 15.978 −2.673 73.209 1.00 0.00 xxxx 1585 ATOM 1586 CG GLU A 203 14.941 −3.342 72.310 1.00 0.00 xxxx 1586 ATOM 1587 CD GLU A 203 15.505 −4.464 71.460 1.00 0.00 xxxx 1587 ATOM 1588 OE1 GLU A 203 16.743 −4.593 71.349 1.00 0.00 xxxx 1588 ATOM 1589 OE2 GLU A 203 14.699 −5.228 70.893 1.00 0.00 xxxx 1589 ATOM 1590 N ALA A 204 17.064 0.210 74.739 1.00 0.00 xxxx 1590 ATOM 1591 CA ALA A 204 18.049 0.717 75.685 1.00 0.00 xxxx 1591 ATOM 1592 C ALA A 204 18.211 2.210 75.445 1.00 0.00 xxxx 1592 ATOM 1593 O ALA A 204 18.120 2.675 74.308 1.00 0.00 xxxx 1593 ATOM 1594 CB ALA A 204 19.400 0.028 75.483 1.00 0.00 xxxx 1594 ATOM 1595 N VAL A 205 18.470 2.955 76.520 1.00 0.00 xxxx 1595 ATOM 1596 CA VAL A 205 18.690 4.399 76.447 1.00 0.00 xxxx 1596 ATOM 1597 C VAL A 205 20.029 4.721 77.097 1.00 0.00 xxxx 1597 ATOM 1598 O VAL A 205 20.225 4.455 78.288 1.00 0.00 xxxx 1598 ATOM 1599 CB VAL A 205 17.566 5.182 77.147 1.00 0.00 xxxx 1599 ATOM 1600 CG1 VAL A 205 17.870 6.677 77.115 1.00 0.00 xxxx 1600 ATOM 1601 CG2 VAL A 205 16.203 4.854 76.517 1.00 0.00 xxxx 1601 ATOM 1602 N PHE A 206 20.919 5.354 76.337 1.00 0.00 xxxx 1602 ATOM 1603 CA PHE A 206 22.159 5.899 76.870 1.00 0.00 xxxx 1603 ATOM 1604 C PHE A 206 22.051 7.414 76.907 1.00 0.00 xxxx 1604 ATOM 1605 O PHE A 206 21.570 8.028 75.954 1.00 0.00 xxxx 1605 ATOM 1606 CB PHE A 206 23.337 5.550 75.956 1.00 0.00 xxxx 1606 ATOM 1607 CG PHE A 206 23.627 4.061 75.837 1.00 0.00 xxxx 1607 ATOM 1608 CD1 PHE A 206 24.652 3.482 76.557 1.00 0.00 xxxx 1608 ATOM 1609 CD2 PHE A 206 22.889 3.258 74.969 1.00 0.00 xxxx 1609 ATOM 1610 CE1 PHE A 206 24.937 2.113 76.419 1.00 0.00 xxxx 1610 ATOM 1611 CE2 PHE A 206 23.158 1.899 74.835 1.00 0.00 xxxx 1611 ATOM 1612 CZ PHE A 206 24.180 1.336 75.555 1.00 0.00 xxxx 1612 ATOM 1613 N ALA A 207 22.503 8.018 78.005 1.00 0.00 xxxx 1613 ATOM 1614 CA ALA A 207 22.572 9.470 78.099 1.00 0.00 xxxx 1614 ATOM 1615 C ALA A 207 23.937 9.866 78.637 1.00 0.00 xxxx 1615 ATOM 1616 O ALA A 207 24.471 9.208 79.539 1.00 0.00 xxxx 1616 ATOM 1617 CB ALA A 207 21.467 10.027 79.005 1.00 0.00 xxxx 1617 ATOM 1618 N ASN A 208 24.498 10.944 78.082 1.00 0.00 xxxx 1618 ATOM 1619 CA ASN A 208 25.825 11.375 78.507 1.00 0.00 xxxx 1619 ATOM 1620 C ASN A 208 25.850 11.893 79.944 1.00 0.00 xxxx 1620 ATOM 1621 O ASN A 208 26.935 11.977 80.516 1.00 0.00 xxxx 1621 ATOM 1622 CB ASN A 208 26.378 12.499 77.614 1.00 0.00 xxxx 1622 ATOM 1623 CG ASN A 208 26.794 12.066 76.190 1.00 0.00 xxxx 1623 ATOM 1624 OD1 ASN A 208 27.122 12.946 75.398 1.00 0.00 xxxx 1624 ATOM 1625 ND2 ASN A 208 26.799 10.770 75.868 1.00 0.00 xxxx 1625 ATOM 1626 N ASN A 209 24.720 12.312 80.515 1.00 0.00 xxxx 1626 ATOM 1627 CA ASN A 209 24.716 12.706 81.922 1.00 0.00 xxxx 1627 ATOM 1628 C ASN A 209 23.396 12.327 82.587 1.00 0.00 xxxx 1628 ATOM 1629 O ASN A 209 22.425 11.927 81.931 1.00 0.00 xxxx 1629 ATOM 1630 CB ASN A 209 25.102 14.184 82.128 1.00 0.00 xxxx 1630 ATOM 1631 CG ASN A 209 23.948 15.150 81.859 1.00 0.00 xxxx 1631 ATOM 1632 OD1 ASN A 209 22.944 14.798 81.229 1.00 0.00 xxxx 1632 ATOM 1633 ND2 ASN A 209 24.091 16.374 82.348 1.00 0.00 xxxx 1633 ATOM 1634 N ASP A 210 23.383 12.465 83.917 1.00 0.00 xxxx 1634 ATOM 1635 CA ASP A 210 22.205 12.098 84.697 1.00 0.00 xxxx 1635 ATOM 1636 C ASP A 210 21.016 12.992 84.382 1.00 0.00 xxxx 1636 ATOM 1637 O ASP A 210 19.892 12.496 84.280 1.00 0.00 xxxx 1637 ATOM 1638 CB ASP A 210 22.499 12.120 86.200 1.00 0.00 xxxx 1638 ATOM 1639 CG ASP A 210 23.228 10.885 86.679 1.00 0.00 xxxx 1639 ATOM 1640 OD1 ASP A 210 23.451 9.951 85.873 1.00 0.00 xxxx 1640 ATOM 1641 OD2 ASP A 210 23.550 10.846 87.885 1.00 0.00 xxxx 1641 ATOM 1642 N ASP A 211 21.228 14.304 84.218 1.00 0.00 xxxx 1642 ATOM 1643 CA ASP A 211 20.071 15.166 83.960 1.00 0.00 xxxx 1643 ATOM 1644 C ASP A 211 19.346 14.769 82.678 1.00 0.00 xxxx 1644 ATOM 1645 O ASP A 211 18.109 14.733 82.643 1.00 0.00 xxxx 1645 ATOM 1646 CB ASP A 211 20.456 16.641 83.956 1.00 0.00 xxxx 1646 ATOM 1647 CG ASP A 211 20.279 17.293 85.323 1.00 0.00 xxxx 1647 ATOM 1648 OD1 ASP A 211 19.754 16.629 86.253 1.00 0.00 xxxx 1648 ATOM 1649 OD2 ASP A 211 20.643 18.479 85.456 1.00 0.00 xxxx 1649 ATOM 1650 N MET A 212 20.089 14.423 81.627 1.00 0.00 xxxx 1650 ATOM 1651 CA MET A 212 19.418 13.970 80.413 1.00 0.00 xxxx 1651 ATOM 1652 C MET A 212 18.766 12.608 80.614 1.00 0.00 xxxx 1652 ATOM 1653 O MET A 212 17.664 12.359 80.105 1.00 0.00 xxxx 1653 ATOM 1654 CB MET A 212 20.388 13.937 79.232 1.00 0.00 xxxx 1654 ATOM 1655 CG MET A 212 20.811 15.334 78.819 1.00 0.00 xxxx 1655 ATOM 1656 SD MET A 212 21.785 15.350 77.315 1.00 0.00 xxxx 1656 ATOM 1657 CE MET A 212 23.183 14.347 77.803 1.00 0.00 xxxx 1657 ATOM 1658 N ALA A 213 19.418 11.707 81.356 1.00 0.00 xxxx 1658 ATOM 1659 CA ALA A 213 18.786 10.419 81.642 1.00 0.00 xxxx 1659 ATOM 1660 C ALA A 213 17.469 10.612 82.378 1.00 0.00 xxxx 1660 ATOM 1661 O ALA A 213 16.484 9.916 82.096 1.00 0.00 xxxx 1661 ATOM 1662 CB ALA A 213 19.728 9.536 82.462 1.00 0.00 xxxx 1662 ATOM 1663 N LEU A 214 17.433 11.567 83.311 1.00 0.00 xxxx 1663 ATOM 1664 CA LEU A 214 16.230 11.827 84.099 1.00 0.00 xxxx 1664 ATOM 1665 C LEU A 214 15.123 12.421 83.242 1.00 0.00 xxxx 1665 ATOM 1666 O LEU A 214 13.948 12.090 83.429 1.00 0.00 xxxx 1666 ATOM 1667 CB LEU A 214 16.562 12.751 85.271 1.00 0.00 xxxx 1667 ATOM 1668 CG LEU A 214 17.503 12.139 86.310 1.00 0.00 xxxx 1668 ATOM 1669 CD1 LEU A 214 18.009 13.201 87.272 1.00 0.00 xxxx 1669 ATOM 1670 CD2 LEU A 214 16.789 11.031 87.065 1.00 0.00 xxxx 1670 ATOM 1671 N GLY A 215 15.471 13.308 82.309 1.00 0.00 xxxx 1671 ATOM 1672 CA GLY A 215 14.475 13.776 81.359 1.00 0.00 xxxx 1672 ATOM 1673 C GLY A 215 13.929 12.650 80.503 1.00 0.00 xxxx 1673 ATOM 1674 O GLY A 215 12.723 12.584 80.244 1.00 0.00 xxxx 1674 ATOM 1675 N ALA A 216 14.806 11.757 80.039 1.00 0.00 xxxx 1675 ATOM 1676 CA ALA A 216 14.338 10.602 79.279 1.00 0.00 xxxx 1676 ATOM 1677 C ALA A 216 13.396 9.751 80.110 1.00 0.00 xxxx 1677 ATOM 1678 O ALA A 216 12.360 9.292 79.612 1.00 0.00 xxxx 1678 ATOM 1679 CB ALA A 216 15.529 9.769 78.802 1.00 0.00 xxxx 1679 ATOM 1680 N ILE A 217 13.738 9.538 81.385 1.00 0.00 xxxx 1680 ATOM 1681 CA ILE A 217 12.897 8.739 82.277 1.00 0.00 xxxx 1681 ATOM 1682 C ILE A 217 11.510 9.355 82.420 1.00 0.00 xxxx 1682 ATOM 1683 O ILE A 217 10.499 8.646 82.418 1.00 0.00 xxxx 1683 ATOM 1684 CB ILE A 217 13.605 8.537 83.627 1.00 0.00 xxxx 1684 ATOM 1685 CG1 ILE A 217 14.716 7.494 83.461 1.00 0.00 xxxx 1685 ATOM 1686 CG2 ILE A 217 12.598 8.125 84.691 1.00 0.00 xxxx 1686 ATOM 1687 CD1 ILE A 217 15.733 7.486 84.585 1.00 0.00 xxxx 1687 ATOM 1688 N GLU A 218 11.430 10.685 82.521 1.00 0.00 xxxx 1688 ATOM 1689 CA GLU A 218 10.119 11.329 82.600 1.00 0.00 xxxx 1689 ATOM 1690 C GLU A 218 9.289 11.080 81.342 1.00 0.00 xxxx 1690 ATOM 1691 O GLU A 218 8.080 10.843 81.427 1.00 0.00 xxxx 1691 ATOM 1692 CB GLU A 218 10.273 12.826 82.880 1.00 0.00 xxxx 1692 ATOM 1693 CG GLU A 218 10.768 13.106 84.295 1.00 0.00 xxxx 1693 ATOM 1694 CD GLU A 218 9.954 12.360 85.351 1.00 0.00 xxxx 1694 ATOM 1695 OE1 GLU A 218 8.711 12.546 85.409 1.00 0.00 xxxx 1695 ATOM 1696 OE2 GLU A 218 10.550 11.574 86.125 1.00 0.00 xxxx 1696 ATOM 1697 N ALA A 219 9.917 11.127 80.162 1.00 0.00 xxxx 1697 ATOM 1698 CA ALA A 219 9.177 10.831 78.937 1.00 0.00 xxxx 1698 ATOM 1699 C ALA A 219 8.754 9.368 78.887 1.00 0.00 xxxx 1699 ATOM 1700 O ALA A 219 7.645 9.048 78.448 1.00 0.00 xxxx 1700 ATOM 1701 CB ALA A 219 10.025 11.184 77.715 1.00 0.00 xxxx 1701 ATOM 1702 N LEU A 220 9.623 8.468 79.358 1.00 0.00 xxxx 1702 ATOM 1703 CA LEU A 220 9.266 7.051 79.431 1.00 0.00 xxxx 1703 ATOM 1704 C LEU A 220 8.105 6.809 80.392 1.00 0.00 xxxx 1704 ATOM 1705 O LEU A 220 7.181 6.049 80.078 1.00 0.00 xxxx 1705 ATOM 1706 CB LEU A 220 10.492 6.229 79.828 1.00 0.00 xxxx 1706 ATOM 1707 CG LEU A 220 11.577 6.146 78.748 1.00 0.00 xxxx 1707 ATOM 1708 CD1 LEU A 220 12.935 5.811 79.350 1.00 0.00 xxxx 1708 ATOM 1709 CD2 LEU A 220 11.184 5.099 77.725 1.00 0.00 xxxx 1709 ATOM 1710 N LYS A 221 8.129 7.452 81.566 1.00 0.00 xxxx 1710 ATOM 1711 CA LYS A 221 7.009 7.320 82.497 1.00 0.00 xxxx 1711 ATOM 1712 C LYS A 221 5.709 7.782 81.858 1.00 0.00 xxxx 1712 ATOM 1713 O LYS A 221 4.675 7.119 81.991 1.00 0.00 xxxx 1713 ATOM 1714 CB LYS A 221 7.284 8.142 83.756 1.00 0.00 xxxx 1714 ATOM 1715 CG LYS A 221 8.319 7.544 84.684 1.00 0.00 xxxx 1715 ATOM 1716 CD LYS A 221 8.604 8.504 85.825 1.00 0.00 xxxx 1716 ATOM 1717 CE LYS A 221 9.505 7.891 86.871 1.00 0.00 xxxx 1717 ATOM 1718 NZ LYS A 221 9.758 8.870 87.968 1.00 0.00 xxxx 1718 ATOM 1719 N SER A 222 5.750 8.912 81.144 1.00 0.00 xxxx 1719 ATOM 1720 CA SER A 222 4.546 9.442 80.517 1.00 0.00 xxxx 1720 ATOM 1721 C SER A 222 3.975 8.470 79.493 1.00 0.00 xxxx 1721 ATOM 1722 O SER A 222 2.756 8.427 79.292 1.00 0.00 xxxx 1722 ATOM 1723 CB SER A 222 4.887 10.783 79.868 1.00 0.00 xxxx 1723 ATOM 1724 OG SER A 222 3.742 11.388 79.291 1.00 0.00 xxxx 1724 ATOM 1725 N ALA A 223 4.835 7.670 78.859 1.00 0.00 xxxx 1725 ATOM 1726 CA ALA A 223 4.440 6.652 77.894 1.00 0.00 xxxx 1726 ATOM 1727 C ALA A 223 4.151 5.298 78.533 1.00 0.00 xxxx 1727 ATOM 1728 O ALA A 223 3.934 4.323 77.806 1.00 0.00 xxxx 1728 ATOM 1729 CB ALA A 223 5.525 6.498 76.820 1.00 0.00 xxxx 1729 ATOM 1730 N GLY A 224 4.168 5.203 79.857 1.00 0.00 xxxx 1730 ATOM 1731 CA GLY A 224 3.714 4.007 80.540 1.00 0.00 xxxx 1731 ATOM 1732 C GLY A 224 4.788 3.065 81.044 1.00 0.00 xxxx 1732 ATOM 1733 O GLY A 224 4.453 1.960 81.485 1.00 0.00 xxxx 1733 ATOM 1734 N TYR A 225 6.059 3.453 80.996 1.00 0.00 xxxx 1734 ATOM 1735 CA TYR A 225 7.105 2.588 81.524 1.00 0.00 xxxx 1735 ATOM 1736 C TYR A 225 7.240 2.767 83.030 1.00 0.00 xxxx 1736 ATOM 1737 O TYR A 225 6.821 3.775 83.605 1.00 0.00 xxxx 1737 ATOM 1738 CB TYR A 225 8.454 2.918 80.882 1.00 0.00 xxxx 1738 ATOM 1739 CG TYR A 225 8.570 2.480 79.443 1.00 0.00 xxxx 1739 ATOM 1740 CD1 TYR A 225 8.000 3.229 78.424 1.00 0.00 xxxx 1740 ATOM 1741 CD2 TYR A 225 9.239 1.309 79.106 1.00 0.00 xxxx 1741 ATOM 1742 CE1 TYR A 225 8.099 2.830 77.102 1.00 0.00 xxxx 1742 ATOM 1743 CE2 TYR A 225 9.345 0.901 77.786 1.00 0.00 xxxx 1743 ATOM 1744 CZ TYR A 225 8.774 1.667 76.790 1.00 0.00 xxxx 1744 ATOM 1745 OH TYR A 225 8.868 1.275 75.474 1.00 0.00 xxxx 1745 ATOM 1746 N PHE A 226 7.838 1.757 83.665 1.00 0.00 xxxx 1746 ATOM 1747 CA PHE A 226 8.172 1.755 85.089 1.00 0.00 xxxx 1747 ATOM 1748 C PHE A 226 6.955 1.612 85.993 1.00 0.00 xxxx 1748 ATOM 1749 O PHE A 226 7.021 1.935 87.183 1.00 0.00 xxxx 1749 ATOM 1750 CB PHE A 226 9.049 2.945 85.479 1.00 0.00 xxxx 1750 ATOM 1751 CG PHE A 226 10.263 3.081 84.613 1.00 0.00 xxxx 1751 ATOM 1752 CD1 PHE A 226 11.193 2.054 84.551 1.00 0.00 xxxx 1752 ATOM 1753 CD2 PHE A 226 10.472 4.221 83.846 1.00 0.00 xxxx 1753 ATOM 1754 CE1 PHE A 226 12.318 2.161 83.746 1.00 0.00 xxxx 1754 ATOM 1755 CE2 PHE A 226 11.592 4.336 83.036 1.00 0.00 xxxx 1755 ATOM 1756 CZ PHE A 226 12.521 3.300 82.988 1.00 0.00 xxxx 1756 ATOM 1757 N THR A 227 5.843 1.150 85.430 1.00 0.00 xxxx 1757 ATOM 1758 CA THR A 227 4.682 0.684 86.169 1.00 0.00 xxxx 1758 ATOM 1759 C THR A 227 4.250 −0.624 85.528 1.00 0.00 xxxx 1759 ATOM 1760 O THR A 227 4.433 −0.828 84.324 1.00 0.00 xxxx 1760 ATOM 1761 CB THR A 227 3.523 1.686 86.088 1.00 0.00 xxxx 1761 ATOM 1762 OG1 THR A 227 3.120 1.844 84.721 1.00 0.00 xxxx 1762 ATOM 1763 CG2 THR A 227 3.933 3.041 86.656 1.00 0.00 xxxx 1763 ATOM 1764 N GLY A 228 3.678 −1.510 86.331 1.00 0.00 xxxx 1764 ATOM 1765 CA GLY A 228 3.389 −2.839 85.817 1.00 0.00 xxxx 1765 ATOM 1766 C GLY A 228 4.687 −3.566 85.519 1.00 0.00 xxxx 1766 ATOM 1767 O GLY A 228 5.616 −3.577 86.333 1.00 0.00 xxxx 1767 ATOM 1768 N ASN A 229 4.770 −4.170 84.336 1.00 0.00 xxxx 1768 ATOM 1769 CA ASN A 229 5.949 −4.930 83.939 1.00 0.00 xxxx 1769 ATOM 1770 C ASN A 229 6.702 −4.298 82.773 1.00 0.00 xxxx 1770 ATOM 1771 O ASN A 229 7.568 −4.953 82.181 1.00 0.00 xxxx 1771 ATOM 1772 CB ASN A 229 5.568 −6.377 83.610 1.00 0.00 xxxx 1772 ATOM 1773 CG ASN A 229 4.838 −7.063 84.752 1.00 0.00 xxxx 1773 ATOM 1774 OD1 ASN A 229 3.804 −7.703 84.550 1.00 0.00 xxxx 1774 ATOM 1775 ND2 ASN A 229 5.372 −6.928 85.962 1.00 0.00 xxxx 1775 ATOM 1776 N LYS A 230 6.405 −3.042 82.438 1.00 0.00 xxxx 1776 ATOM 1777 CA LYS A 230 6.967 −2.385 81.260 1.00 0.00 xxxx 1777 ATOM 1778 C LYS A 230 8.247 −1.659 81.660 1.00 0.00 xxxx 1778 ATOM 1779 O LYS A 230 8.196 −0.602 82.292 1.00 0.00 xxxx 1779 ATOM 1780 CB LYS A 230 5.952 −1.404 80.685 1.00 0.00 xxxx 1780 ATOM 1781 CG LYS A 230 6.277 −0.908 79.292 1.00 0.00 xxxx 1781 ATOM 1782 CD LYS A 230 5.185 0.026 78.796 1.00 0.00 xxxx 1782 ATOM 1783 CE LYS A 230 5.326 0.329 77.315 1.00 0.00 xxxx 1783 ATOM 1784 NZ LYS A 230 4.308 1.323 76.869 1.00 0.00 xxxx 1784 ATOM 1785 N TYR A 231 9.391 −2.211 81.264 1.00 0.00 xxxx 1785 ATOM 1786 CA TYR A 231 10.690 −1.754 81.735 1.00 0.00 xxxx 1786 ATOM 1787 C TYR A 231 11.625 −1.492 80.561 1.00 0.00 xxxx 1787 ATOM 1788 O TYR A 231 11.531 −2.142 79.519 1.00 0.00 xxxx 1788 ATOM 1789 CB TYR A 231 11.305 −2.813 82.651 1.00 0.00 xxxx 1789 ATOM 1790 CG TYR A 231 12.673 −2.447 83.152 1.00 0.00 xxxx 1790 ATOM 1791 CD1 TYR A 231 12.824 −1.635 84.264 1.00 0.00 xxxx 1791 ATOM 1792 CD2 TYR A 231 13.814 −2.906 82.508 1.00 0.00 xxxx 1792 ATOM 1793 CE1 TYR A 231 14.077 −1.293 84.726 1.00 0.00 xxxx 1793 ATOM 1794 CE2 TYR A 231 15.065 −2.574 82.960 1.00 0.00 xxxx 1794 ATOM 1795 CZ TYR A 231 15.197 −1.764 84.060 1.00 0.00 xxxx 1795 ATOM 1796 OH TYR A 231 16.452 −1.437 84.506 1.00 0.00 xxxx 1796 ATOM 1797 N ILE A 232 12.542 −0.539 80.740 1.00 0.00 xxxx 1797 ATOM 1798 CA ILE A 232 13.594 −0.267 79.760 1.00 0.00 xxxx 1798 ATOM 1799 C ILE A 232 14.838 0.172 80.524 1.00 0.00 xxxx 1799 ATOM 1800 O ILE A 232 14.719 0.936 81.494 1.00 0.00 xxxx 1800 ATOM 1801 CB ILE A 232 13.147 0.780 78.728 1.00 0.00 xxxx 1801 ATOM 1802 CG1 ILE A 232 14.186 0.924 77.622 1.00 0.00 xxxx 1802 ATOM 1803 CG2 ILE A 232 12.864 2.122 79.397 1.00 0.00 xxxx 1803 ATOM 1804 CD1 ILE A 232 13.684 1.726 76.428 1.00 0.00 xxxx 1804 ATOM 1805 N PRO A 233 16.035 −0.298 80.160 1.00 0.00 xxxx 1805 ATOM 1806 CA PRO A 233 17.246 0.122 80.880 1.00 0.00 xxxx 1806 ATOM 1807 C PRO A 233 17.726 1.475 80.372 1.00 0.00 xxxx 1807 ATOM 1808 O PRO A 233 17.838 1.700 79.163 1.00 0.00 xxxx 1808 ATOM 1809 CB PRO A 233 18.260 −0.975 80.535 1.00 0.00 xxxx 1809 ATOM 1810 CG PRO A 233 17.816 −1.455 79.173 1.00 0.00 xxxx 1810 ATOM 1811 CD PRO A 233 16.306 −1.417 79.237 1.00 0.00 xxxx 1811 ATOM 1812 N VAL A 234 18.000 2.378 81.311 1.00 0.00 xxxx 1812 ATOM 1813 CA VAL A 234 18.495 3.726 81.046 1.00 0.00 xxxx 1813 ATOM 1814 C VAL A 234 19.765 3.893 81.869 1.00 0.00 xxxx 1814 ATOM 1815 O VAL A 234 19.782 3.535 83.053 1.00 0.00 xxxx 1815 ATOM 1816 CB VAL A 234 17.460 4.778 81.487 1.00 0.00 xxxx 1816 ATOM 1817 CG1 VAL A 234 17.978 6.191 81.195 1.00 0.00 xxxx 1817 ATOM 1818 CG2 VAL A 234 16.112 4.530 80.804 1.00 0.00 xxxx 1818 ATOM 1819 N VAL A 235 20.823 4.394 81.240 1.00 0.00 xxxx 1819 ATOM 1820 CA VAL A 235 22.057 4.675 81.959 1.00 0.00 xxxx 1820 ATOM 1821 C VAL A 235 22.430 6.139 81.791 1.00 0.00 xxxx 1821 ATOM 1822 O VAL A 235 22.133 6.778 80.774 1.00 0.00 xxxx 1822 ATOM 1823 CB VAL A 235 23.217 3.756 81.523 1.00 0.00 xxxx 1823 ATOM 1824 CG1 VAL A 235 22.953 2.340 81.988 1.00 0.00 xxxx 1824 ATOM 1825 CG2 VAL A 235 23.378 3.811 80.029 1.00 0.00 xxxx 1825 ATOM 1826 N GLY A 236 23.088 6.666 82.819 1.00 0.00 xxxx 1826 ATOM 1827 CA GLY A 236 23.609 8.026 82.778 1.00 0.00 xxxx 1827 ATOM 1828 C GLY A 236 25.040 8.151 83.282 1.00 0.00 xxxx 1828 ATOM 1829 O GLY A 236 25.756 7.147 83.372 1.00 0.00 xxxx 1829 ATOM 1830 N VAL A 237 25.485 9.375 83.586 1.00 0.00 xxxx 1830 ATOM 1831 CA VAL A 237 26.766 9.634 84.252 1.00 0.00 xxxx 1831 ATOM 1832 C VAL A 237 26.558 10.798 85.209 1.00 0.00 xxxx 1832 ATOM 1833 O VAL A 237 25.967 11.808 84.815 1.00 0.00 xxxx 1833 ATOM 1834 CB VAL A 237 27.894 10.024 83.266 1.00 0.00 xxxx 1834 ATOM 1835 CG1 VAL A 237 29.137 10.427 84.038 1.00 0.00 xxxx 1835 ATOM 1836 CG2 VAL A 237 28.220 8.897 82.312 1.00 0.00 xxxx 1836 ATOM 1837 N ASP A 238 27.024 10.642 86.462 1.00 0.00 xxxx 1837 ATOM 1838 CA ASP A 238 27.345 11.681 87.450 1.00 0.00 xxxx 1838 ATOM 1839 C ASP A 238 27.114 11.178 88.868 1.00 0.00 xxxx 1839 ATOM 1840 O ASP A 238 27.899 11.481 89.767 1.00 0.00 xxxx 1840 ATOM 1841 CB ASP A 238 26.536 12.973 87.299 1.00 0.00 xxxx 1841 ATOM 1842 CG ASP A 238 27.067 13.885 86.218 1.00 0.00 xxxx 1842 ATOM 1843 OD1 ASP A 238 28.247 13.776 85.824 1.00 0.00 xxxx 1843 ATOM 1844 OD2 ASP A 238 26.279 14.734 85.762 1.00 0.00 xxxx 1844 ATOM 1845 N ALA A 239 26.025 10.432 89.073 1.00 0.00 xxxx 1845 ATOM 1846 CA ALA A 239 25.549 10.070 90.408 1.00 0.00 xxxx 1846 ATOM 1847 C ALA A 239 25.271 11.317 91.243 1.00 0.00 xxxx 1847 ATOM 1848 O ALA A 239 25.662 11.417 92.406 1.00 0.00 xxxx 1848 ATOM 1849 CB ALA A 239 26.493 9.092 91.121 1.00 0.00 xxxx 1849 ATOM 1850 N THR A 240 24.590 12.283 90.626 1.00 0.00 xxxx 1850 ATOM 1851 CA THR A 240 24.058 13.399 91.396 1.00 0.00 xxxx 1851 ATOM 1852 C THR A 240 22.968 12.895 92.340 1.00 0.00 xxxx 1852 ATOM 1853 O THR A 240 22.496 11.758 92.239 1.00 0.00 xxxx 1853 ATOM 1854 CB THR A 240 23.417 14.440 90.476 1.00 0.00 xxxx 1854 ATOM 1855 OG1 THR A 240 22.331 13.837 89.764 1.00 0.00 xxxx 1855 ATOM 1856 CG2 THR A 240 24.422 15.016 89.473 1.00 0.00 xxxx 1856 ATOM 1857 N ALA A 241 22.542 13.762 93.258 1.00 0.00 xxxx 1857 ATOM 1858 CA ALA A 241 21.444 13.384 94.147 1.00 0.00 xxxx 1858 ATOM 1859 C ALA A 241 20.197 12.922 93.397 1.00 0.00 xxxx 1859 ATOM 1860 O ALA A 241 19.662 11.858 93.744 1.00 0.00 xxxx 1860 ATOM 1861 CB ALA A 241 21.143 14.492 95.165 1.00 0.00 xxxx 1861 ATOM 1862 N PRO A 242 19.696 13.626 92.375 1.00 0.00 xxxx 1862 ATOM 1863 CA PRO A 242 18.529 13.084 91.664 1.00 0.00 xxxx 1863 ATOM 1864 C PRO A 242 18.840 11.821 90.880 1.00 0.00 xxxx 1864 ATOM 1865 O PRO A 242 17.951 10.979 90.725 1.00 0.00 xxxx 1865 ATOM 1866 CB PRO A 242 18.056 14.241 90.771 1.00 0.00 xxxx 1866 ATOM 1867 CG PRO A 242 19.187 15.185 90.708 1.00 0.00 xxxx 1867 ATOM 1868 CD PRO A 242 20.012 15.003 91.949 1.00 0.00 xxxx 1868 ATOM 1869 N GLY A 243 20.072 11.652 90.396 1.00 0.00 xxxx 1869 ATOM 1870 CA GLY A 243 20.421 10.405 89.729 1.00 0.00 xxxx 1870 ATOM 1871 C GLY A 243 20.411 9.234 90.694 1.00 0.00 xxxx 1871 ATOM 1872 O GLY A 243 19.869 8.164 90.392 1.00 0.00 xxxx 1872 ATOM 1873 N ILE A 244 20.995 9.423 91.880 1.00 0.00 xxxx 1873 ATOM 1874 CA ILE A 244 20.952 8.389 92.913 1.00 0.00 xxxx 1874 ATOM 1875 C ILE A 244 19.513 8.030 93.257 1.00 0.00 xxxx 1875 ATOM 1876 O ILE A 244 19.168 6.850 93.408 1.00 0.00 xxxx 1876 ATOM 1877 CB ILE A 244 21.745 8.848 94.148 1.00 0.00 xxxx 1877 ATOM 1878 CG1 ILE A 244 23.233 8.926 93.802 1.00 0.00 xxxx 1878 ATOM 1879 CG2 ILE A 244 21.491 7.935 95.335 1.00 0.00 xxxx 1879 ATOM 1880 CD1 ILE A 244 24.048 9.638 94.852 1.00 0.00 xxxx 1880 ATOM 1881 N GLN A 245 18.644 9.036 93.363 1.00 0.00 xxxx 1881 ATOM 1882 CA GLN A 245 17.257 8.751 93.706 1.00 0.00 xxxx 1882 ATOM 1883 C GLN A 245 16.587 7.904 92.626 1.00 0.00 xxxx 1883 ATOM 1884 O GLN A 245 15.791 7.013 92.938 1.00 0.00 xxxx 1884 ATOM 1885 CB GLN A 245 16.496 10.053 93.937 1.00 0.00 xxxx 1885 ATOM 1886 CG GLN A 245 15.085 9.835 94.443 1.00 0.00 xxxx 1886 ATOM 1887 CD GLN A 245 15.060 9.092 95.773 1.00 0.00 xxxx 1887 ATOM 1888 OE1 GLN A 245 15.750 9.467 96.722 1.00 0.00 xxxx 1888 ATOM 1889 NE2 GLN A 245 14.295 8.014 95.832 1.00 0.00 xxxx 1889 ATOM 1890 N ALA A 246 16.919 8.145 91.353 1.00 0.00 xxxx 1890 ATOM 1891 CA ALA A 246 16.345 7.341 90.279 1.00 0.00 xxxx 1891 ATOM 1892 C ALA A 246 16.863 5.904 90.301 1.00 0.00 xxxx 1892 ATOM 1893 O ALA A 246 16.121 4.980 89.942 1.00 0.00 xxxx 1893 ATOM 1894 CB ALA A 246 16.582 8.001 88.924 1.00 0.00 xxxx 1894 ATOM 1895 N ILE A 247 18.113 5.690 90.717 1.00 0.00 xxxx 1895 ATOM 1896 CA ILE A 247 18.587 4.325 90.955 1.00 0.00 xxxx 1896 ATOM 1897 C ILE A 247 17.725 3.647 92.016 1.00 0.00 xxxx 1897 ATOM 1898 O ILE A 247 17.258 2.514 91.840 1.00 0.00 xxxx 1898 ATOM 1899 CB ILE A 247 20.070 4.327 91.361 1.00 0.00 xxxx 1899 ATOM 1900 CG1 ILE A 247 20.940 4.927 90.259 1.00 0.00 xxxx 1900 ATOM 1901 CG2 ILE A 247 20.533 2.903 91.692 1.00 0.00 xxxx 1901 ATOM 1902 CD1 ILE A 247 21.292 3.964 89.184 1.00 0.00 xxxx 1902 ATOM 1903 N LYS A 248 17.490 4.342 93.134 1.00 0.00 xxxx 1903 ATOM 1904 CA LYS A 248 16.681 3.779 94.214 1.00 0.00 xxxx 1904 ATOM 1905 C LYS A 248 15.234 3.559 93.784 1.00 0.00 xxxx 1905 ATOM 1906 O LYS A 248 14.592 2.608 94.245 1.00 0.00 xxxx 1906 ATOM 1907 CB LYS A 248 16.728 4.699 95.431 1.00 0.00 xxxx 1907 ATOM 1908 CG LYS A 248 18.108 4.863 96.041 1.00 0.00 xxxx 1908 ATOM 1909 CD LYS A 248 18.059 5.846 97.200 1.00 0.00 xxxx 1909 ATOM 1910 CE LYS A 248 19.406 5.968 97.881 1.00 0.00 xxxx 1910 ATOM 1911 NZ LYS A 248 19.339 6.962 98.994 1.00 0.00 xxxx 1911 ATOM 1912 N ASP A 249 14.709 4.416 92.901 1.00 0.00 xxxx 1912 ATOM 1913 CA ASP A 249 13.350 4.285 92.385 1.00 0.00 xxxx 1913 ATOM 1914 C ASP A 249 13.212 3.147 91.379 1.00 0.00 xxxx 1914 ATOM 1915 O ASP A 249 12.078 2.765 91.056 1.00 0.00 xxxx 1915 ATOM 1916 CB ASP A 249 12.911 5.580 91.688 1.00 0.00 xxxx 1916 ATOM 1917 CG ASP A 249 12.763 6.758 92.637 1.00 0.00 xxxx 1917 ATOM 1918 OD1 ASP A 249 12.696 6.548 93.866 1.00 0.00 xxxx 1918 ATOM 1919 OD2 ASP A 249 12.697 7.906 92.134 1.00 0.00 xxxx 1919 ATOM 1920 N GLY A 250 14.319 2.612 90.869 1.00 0.00 xxxx 1920 ATOM 1921 CA GLY A 250 14.265 1.554 89.881 1.00 0.00 xxxx 1921 ATOM 1922 C GLY A 250 14.164 2.022 88.441 1.00 0.00 xxxx 1922 ATOM 1923 O GLY A 250 14.071 1.180 87.540 1.00 0.00 xxxx 1923 ATOM 1924 N THR A 251 14.179 3.330 88.194 1.00 0.00 xxxx 1924 ATOM 1925 CA THR A 251 13.998 3.850 86.841 1.00 0.00 xxxx 1925 ATOM 1926 C THR A 251 15.314 4.102 86.118 1.00 0.00 xxxx 1926 ATOM 1927 O THR A 251 15.324 4.183 84.881 1.00 0.00 xxxx 1927 ATOM 1928 CB THR A 251 13.191 5.156 86.889 1.00 0.00 xxxx 1928 ATOM 1929 OG1 THR A 251 13.881 6.094 87.723 1.00 0.00 xxxx 1929 ATOM 1930 CG2 THR A 251 11.778 4.916 87.433 1.00 0.00 xxxx 1930 ATOM 1931 N LEU A 252 16.412 4.249 86.843 1.00 0.00 xxxx 1931 ATOM 1932 CA LEU A 252 17.732 4.400 86.245 1.00 0.00 xxxx 1932 ATOM 1933 C LEU A 252 18.501 3.128 86.565 1.00 0.00 xxxx 1933 ATOM 1934 O LEU A 252 18.624 2.759 87.735 1.00 0.00 xxxx 1934 ATOM 1935 CB LEU A 252 18.432 5.630 86.828 1.00 0.00 xxxx 1935 ATOM 1936 CG LEU A 252 19.763 6.044 86.193 1.00 0.00 xxxx 1936 ATOM 1937 CD1 LEU A 252 19.584 6.416 84.720 1.00 0.00 xxxx 1937 ATOM 1938 CD2 LEU A 252 20.375 7.224 86.963 1.00 0.00 xxxx 1938 ATOM 1939 N LEU A 253 18.960 2.428 85.521 1.00 0.00 xxxx 1939 ATOM 1940 CA LEU A 253 19.663 1.166 85.737 1.00 0.00 xxxx 1940 ATOM 1941 C LEU A 253 21.013 1.394 86.390 1.00 0.00 xxxx 1941 ATOM 1942 O LEU A 253 21.428 0.632 87.277 1.00 0.00 xxxx 1942 ATOM 1943 CB LEU A 253 19.849 0.445 84.402 1.00 0.00 xxxx 1943 ATOM 1944 CG LEU A 253 20.806 −0.752 84.408 1.00 0.00 xxxx 1944 ATOM 1945 CD1 LEU A 253 20.224 −1.883 85.239 1.00 0.00 xxxx 1945 ATOM 1946 CD2 LEU A 253 21.120 −1.217 82.996 1.00 0.00 xxxx 1946 ATOM 1947 N GLY A 254 21.721 2.421 85.957 1.00 0.00 xxxx 1947 ATOM 1948 CA GLY A 254 23.032 2.651 86.518 1.00 0.00 xxxx 1948 ATOM 1949 C GLY A 254 23.542 4.002 86.097 1.00 0.00 xxxx 1949 ATOM 1950 O GLY A 254 23.017 4.642 85.180 1.00 0.00 xxxx 1950 ATOM 1951 N THR A 255 24.595 4.416 86.787 1.00 0.00 xxxx 1951 ATOM 1952 CA THR A 255 25.286 5.638 86.447 1.00 0.00 xxxx 1952 ATOM 1953 C THR A 255 26.754 5.460 86.803 1.00 0.00 xxxx 1953 ATOM 1954 O THR A 255 27.211 4.363 87.144 1.00 0.00 xxxx 1954 ATOM 1955 CB THR A 255 24.607 6.845 87.111 1.00 0.00 xxxx 1955 ATOM 1956 OG1 THR A 255 25.209 8.054 86.631 1.00 0.00 xxxx 1956 ATOM 1957 CG2 THR A 255 24.713 6.788 88.627 1.00 0.00 xxxx 1957 ATOM 1958 N VAL A 256 27.504 6.539 86.670 1.00 0.00 xxxx 1958 ATOM 1959 CA VAL A 256 28.924 6.541 86.956 1.00 0.00 xxxx 1959 ATOM 1960 C VAL A 256 29.165 7.740 87.852 1.00 0.00 xxxx 1960 ATOM 1961 O VAL A 256 28.821 8.862 87.478 1.00 0.00 xxxx 1961 ATOM 1962 CB VAL A 256 29.741 6.649 85.658 1.00 0.00 xxxx 1962 ATOM 1963 CG1 VAL A 256 31.235 6.627 85.977 1.00 0.00 xxxx 1963 ATOM 1964 CG2 VAL A 256 29.356 5.528 84.679 1.00 0.00 xxxx 1964 ATOM 1965 N LEU A 257 29.711 7.504 89.040 1.00 0.00 xxxx 1965 ATOM 1966 CA LEU A 257 30.015 8.606 89.941 1.00 0.00 xxxx 1966 ATOM 1967 C LEU A 257 31.080 9.495 89.321 1.00 0.00 xxxx 1967 ATOM 1968 O LEU A 257 32.188 9.032 89.022 1.00 0.00 xxxx 1968 ATOM 1969 CB LEU A 257 30.487 8.069 91.291 1.00 0.00 xxxx 1969 ATOM 1970 CG LEU A 257 30.976 9.158 92.256 1.00 0.00 xxxx 1970 ATOM 1971 CD1 LEU A 257 29.845 10.097 92.657 1.00 0.00 xxxx 1971 ATOM 1972 CD2 LEU A 257 31.614 8.517 93.481 1.00 0.00 xxxx 1972 ATOM 1973 N ASN A 258 30.718 10.764 89.095 1.00 0.00 xxxx 1973 ATOM 1974 CA ASN A 258 31.640 11.815 88.691 1.00 0.00 xxxx 1974 ATOM 1975 C ASN A 258 31.941 12.557 89.986 1.00 0.00 xxxx 1975 ATOM 1976 O ASN A 258 31.043 13.144 90.596 1.00 0.00 xxxx 1976 ATOM 1977 CB ASN A 258 30.968 12.719 87.655 1.00 0.00 xxxx 1977 ATOM 1978 CG ASN A 258 31.938 13.653 86.968 1.00 0.00 xxxx 1978 ATOM 1979 OD1 ASN A 258 33.139 13.611 87.231 1.00 0.00 xxxx 1979 ATOM 1980 ND2 ASN A 258 31.428 14.497 86.073 1.00 0.00 xxxx 1980 ATOM 1981 N ASP A 259 33.184 12.460 90.442 1.00 0.00 xxxx 1981 ATOM 1982 CA ASP A 259 33.543 12.754 91.829 1.00 0.00 xxxx 1982 ATOM 1983 C ASP A 259 33.747 14.260 91.986 1.00 0.00 xxxx 1983 ATOM 1984 O ASP A 259 34.868 14.780 91.900 1.00 0.00 xxxx 1984 ATOM 1985 CB ASP A 259 34.781 11.940 92.193 1.00 0.00 xxxx 1985 ATOM 1986 CG ASP A 259 35.185 12.071 93.647 1.00 0.00 xxxx 1986 ATOM 1987 OD1 ASP A 259 34.667 12.950 94.362 1.00 0.00 xxxx 1987 ATOM 1988 OD2 ASP A 259 36.067 11.285 94.061 1.00 0.00 xxxx 1988 ATOM 1989 N ALA A 260 32.639 14.961 92.251 1.00 0.00 xxxx 1989 ATOM 1990 CA ALA A 260 32.671 16.414 92.388 1.00 0.00 xxxx 1990 ATOM 1991 C ALA A 260 33.505 16.846 93.584 1.00 0.00 xxxx 1991 ATOM 1992 O ALA A 260 34.188 17.878 93.531 1.00 0.00 xxxx 1992 ATOM 1993 CB ALA A 260 31.246 16.943 92.547 1.00 0.00 xxxx 1993 ATOM 1994 N LYS A 261 33.456 16.085 94.680 1.00 0.00 xxxx 1994 ATOM 1995 CA LYS A 261 34.170 16.493 95.885 1.00 0.00 xxxx 1995 ATOM 1996 C LYS A 261 35.681 16.499 95.667 1.00 0.00 xxxx 1996 ATOM 1997 O LYS A 261 36.364 17.463 96.037 1.00 0.00 xxxx 1997 ATOM 1998 CB LYS A 261 33.771 15.608 97.064 1.00 0.00 xxxx 1998 ATOM 1999 CG LYS A 261 32.314 15.783 97.477 1.00 0.00 xxxx 1999 ATOM 2000 CD LYS A 261 31.976 14.931 98.695 1.00 0.00 xxxx 2000 ATOM 2001 CE LYS A 261 30.512 15.071 99.081 1.00 0.00 xxxx 2001 ATOM 2002 NZ LYS A 261 30.150 16.484 99.379 1.00 0.00 xxxx 2002 ATOM 2003 N ASN A 262 36.227 15.441 95.052 1.00 0.00 xxxx 2003 ATOM 2004 CA ASN A 262 37.666 15.428 94.815 1.00 0.00 xxxx 2004 ATOM 2005 C ASN A 262 38.082 16.350 93.674 1.00 0.00 xxxx 2005 ATOM 2006 O ASN A 262 39.187 16.901 93.721 1.00 0.00 xxxx 2006 ATOM 2007 CB ASN A 262 38.198 14.002 94.643 1.00 0.00 xxxx 2007 ATOM 2008 CG ASN A 262 38.342 13.280 95.971 1.00 0.00 xxxx 2008 ATOM 2009 OD1 ASN A 262 39.094 13.708 96.849 1.00 0.00 xxxx 2009 ATOM 2010 ND2 ASN A 262 37.614 12.190 96.125 1.00 0.00 xxxx 2010 ATOM 2011 N GLN A 263 37.226 16.564 92.668 1.00 0.00 xxxx 2011 ATOM 2012 CA GLN A 263 37.565 17.566 91.657 1.00 0.00 xxxx 2012 ATOM 2013 C GLN A 263 37.590 18.958 92.268 1.00 0.00 xxxx 2013 ATOM 2014 O GLN A 263 38.479 19.759 91.957 1.00 0.00 xxxx 2014 ATOM 2015 CB GLN A 263 36.608 17.491 90.463 1.00 0.00 xxxx 2015 ATOM 2016 CG GLN A 263 36.799 16.209 89.647 1.00 0.00 xxxx 2016 ATOM 2017 CD GLN A 263 35.778 16.030 88.551 1.00 0.00 xxxx 2017 ATOM 2018 OE1 GLN A 263 35.494 16.960 87.787 1.00 0.00 xxxx 2018 ATOM 2019 NE2 GLN A 263 35.240 14.823 88.445 1.00 0.00 xxxx 2019 ATOM 2020 N ALA A 264 36.644 19.248 93.163 1.00 0.00 xxxx 2020 ATOM 2021 CA ALA A 264 36.625 20.545 93.830 1.00 0.00 xxxx 2021 ATOM 2022 C ALA A 264 37.857 20.733 94.698 1.00 0.00 xxxx 2022 ATOM 2023 O ALA A 264 38.449 21.820 94.715 1.00 0.00 xxxx 2023 ATOM 2024 CB ALA A 264 35.364 20.685 94.682 1.00 0.00 xxxx 2024 ATOM 2025 N LYS A 265 38.251 19.688 95.441 1.00 0.00 xxxx 2025 ATOM 2026 CA LYS A 265 39.406 19.798 96.327 1.00 0.00 xxxx 2026 ATOM 2027 C LYS A 265 40.695 19.981 95.537 1.00 0.00 xxxx 2027 ATOM 2028 O LYS A 265 41.549 20.796 95.911 1.00 0.00 xxxx 2028 ATOM 2029 CB LYS A 265 39.493 18.569 97.235 1.00 0.00 xxxx 2029 ATOM 2030 CG LYS A 265 40.520 18.700 98.345 1.00 0.00 xxxx 2030 ATOM 2031 CD LYS A 265 40.489 17.514 99.304 1.00 0.00 xxxx 2031 ATOM 2032 CE LYS A 265 41.232 17.846 100.589 1.00 0.00 xxxx 2032 ATOM 2033 NZ LYS A 265 42.514 18.556 100.318 1.00 0.00 xxxx 2033 ATOM 2034 N ALA A 266 40.855 19.237 94.440 1.00 0.00 xxxx 2034 ATOM 2035 CA ALA A 266 42.049 19.392 93.619 1.00 0.00 xxxx 2035 ATOM 2036 C ALA A 266 42.104 20.779 92.984 1.00 0.00 xxxx 2036 ATOM 2037 O ALA A 266 43.165 21.411 92.952 1.00 0.00 xxxx 2037 ATOM 2038 CB ALA A 266 42.111 18.298 92.553 1.00 0.00 xxxx 2038 ATOM 2039 N THR A 267 40.959 21.279 92.503 1.00 0.00 xxxx 2039 ATOM 2040 CA THR A 267 40.914 22.606 91.884 1.00 0.00 xxxx 2040 ATOM 2041 C THR A 267 41.245 23.686 92.901 1.00 0.00 xxxx 2041 ATOM 2042 O THR A 267 42.079 24.570 92.647 1.00 0.00 xxxx 2042 ATOM 2043 CB THR A 267 39.529 22.864 91.293 1.00 0.00 xxxx 2043 ATOM 2044 OG1 THR A 267 39.235 21.873 90.304 1.00 0.00 xxxx 2044 ATOM 2045 CG2 THR A 267 39.483 24.234 90.627 1.00 0.00 xxxx 2045 ATOM 2046 N PHE A 268 40.600 23.633 94.067 1.00 0.00 xxxx 2046 ATOM 2047 CA PHE A 268 40.922 24.609 95.096 1.00 0.00 xxxx 2047 ATOM 2048 C PHE A 268 42.388 24.525 95.490 1.00 0.00 xxxx 2048 ATOM 2049 O PHE A 268 43.061 25.554 95.609 1.00 0.00 xxxx 2049 ATOM 2050 CB PHE A 268 40.052 24.460 96.344 1.00 0.00 xxxx 2050 ATOM 2051 CG PHE A 268 40.498 25.370 97.436 1.00 0.00 xxxx 2051 ATOM 2052 CD1 PHE A 268 40.176 26.712 97.382 1.00 0.00 xxxx 2052 ATOM 2053 CD2 PHE A 268 41.316 24.920 98.463 1.00 0.00 xxxx 2053 ATOM 2054 CE1 PHE A 268 40.627 27.585 98.350 1.00 0.00 xxxx 2054 ATOM 2055 CE2 PHE A 268 41.770 25.791 99.436 1.00 0.00 xxxx 2055 ATOM 2056 CZ PHE A 268 41.430 27.125 99.382 1.00 0.00 xxxx 2056 ATOM 2057 N ASN A 269 42.891 23.307 95.749 1.00 0.00 xxxx 2057 ATOM 2058 CA ASN A 269 44.260 23.169 96.239 1.00 0.00 xxxx 2058 ATOM 2059 C ASN A 269 45.260 23.728 95.236 1.00 0.00 xxxx 2059 ATOM 2060 O ASN A 269 46.225 24.396 95.627 1.00 0.00 xxxx 2060 ATOM 2061 CB ASN A 269 44.596 21.705 96.537 1.00 0.00 xxxx 2061 ATOM 2062 CG ASN A 269 43.939 21.179 97.797 1.00 0.00 xxxx 2062 ATOM 2063 OD1 ASN A 269 44.044 19.987 98.102 1.00 0.00 xxxx 2063 ATOM 2064 ND2 ASN A 269 43.253 22.045 98.526 1.00 0.00 xxxx 2064 ATOM 2065 N ILE A 270 45.040 23.483 93.939 1.00 0.00 xxxx 2065 ATOM 2066 CA ILE A 270 45.923 24.058 92.923 1.00 0.00 xxxx 2066 ATOM 2067 C ILE A 270 45.859 25.579 92.962 1.00 0.00 xxxx 2067 ATOM 2068 O ILE A 270 46.893 26.259 92.973 1.00 0.00 xxxx 2068 ATOM 2069 CB ILE A 270 45.571 23.517 91.527 1.00 0.00 xxxx 2069 ATOM 2070 CG1 ILE A 270 46.007 22.072 91.408 1.00 0.00 xxxx 2070 ATOM 2071 CG2 ILE A 270 46.236 24.370 90.425 1.00 0.00 xxxx 2071 ATOM 2072 CD1 ILE A 270 45.457 21.393 90.169 1.00 0.00 xxxx 2072 ATOM 2073 N ALA A 271 44.645 26.142 92.967 1.00 0.00 xxxx 2073 ATOM 2074 CA ALA A 271 44.510 27.599 92.969 1.00 0.00 xxxx 2074 ATOM 2075 C ALA A 271 45.108 28.206 94.229 1.00 0.00 xxxx 2075 ATOM 2076 O ALA A 271 45.705 29.292 94.188 1.00 0.00 xxxx 2076 ATOM 2077 CB ALA A 271 43.038 27.994 92.836 1.00 0.00 xxxx 2077 ATOM 2078 N TYR A 272 44.980 27.506 95.354 1.00 0.00 xxxx 2078 ATOM 2079 CA TYR A 272 45.485 28.004 96.629 1.00 0.00 xxxx 2079 ATOM 2080 C TYR A 272 47.012 28.021 96.651 1.00 0.00 xxxx 2080 ATOM 2081 O TYR A 272 47.624 28.977 97.147 1.00 0.00 xxxx 2081 ATOM 2082 CB TYR A 272 44.909 27.125 97.741 1.00 0.00 xxxx 2082 ATOM 2083 CG TYR A 272 45.268 27.495 99.162 1.00 0.00 xxxx 2083 ATOM 2084 CD1 TYR A 272 44.912 28.721 99.698 1.00 0.00 xxxx 2084 ATOM 2085 CD2 TYR A 272 45.916 26.584 99.983 1.00 0.00 xxxx 2085 ATOM 2086 CE1 TYR A 272 45.223 29.047 101.014 1.00 0.00 xxxx 2086 ATOM 2087 CE2 TYR A 272 46.228 26.900 101.296 1.00 0.00 xxxx 2087 ATOM 2088 CZ TYR A 272 45.876 28.133 101.799 1.00 0.00 xxxx 2088 ATOM 2089 OH TYR A 272 46.183 28.458 103.102 1.00 0.00 xxxx 2089 ATOM 2090 N GLU A 273 47.651 26.968 96.126 1.00 0.00 xxxx 2090 ATOM 2091 CA GLU A 273 49.107 26.974 96.051 1.00 0.00 xxxx 2091 ATOM 2092 C GLU A 273 49.592 28.062 95.104 1.00 0.00 xxxx 2092 ATOM 2093 O GLU A 273 50.506 28.826 95.437 1.00 0.00 xxxx 2093 ATOM 2094 CB GLU A 273 49.621 25.598 95.622 1.00 0.00 xxxx 2094 ATOM 2095 CG GLU A 273 49.298 24.482 96.611 1.00 0.00 xxxx 2095 ATOM 2096 CD GLU A 273 49.896 24.718 97.992 1.00 0.00 xxxx 2096 ATOM 2097 OE1 GLU A 273 51.089 25.073 98.078 1.00 0.00 xxxx 2097 ATOM 2098 OE2 GLU A 273 49.168 24.555 98.993 1.00 0.00 xxxx 2098 ATOM 2099 N LEU A 274 48.968 28.165 93.928 1.00 0.00 xxxx 2099 ATOM 2100 CA LEU A 274 49.361 29.188 92.963 1.00 0.00 xxxx 2100 ATOM 2101 C LEU A 274 49.151 30.589 93.519 1.00 0.00 xxxx 2101 ATOM 2102 O LEU A 274 49.959 31.488 93.267 1.00 0.00 xxxx 2102 ATOM 2103 CB LEU A 274 48.577 29.004 91.666 1.00 0.00 xxxx 2103 ATOM 2104 CG LEU A 274 48.907 27.761 90.837 1.00 0.00 xxxx 2104 ATOM 2105 CD1 LEU A 274 47.868 27.549 89.742 1.00 0.00 xxxx 2105 ATOM 2106 CD2 LEU A 274 50.315 27.857 90.249 1.00 0.00 xxxx 2106 ATOM 2107 N ALA A 275 48.073 30.794 94.281 1.00 0.00 xxxx 2107 ATOM 2108 CA ALA A 275 47.819 32.092 94.897 1.00 0.00 xxxx 2108 ATOM 2109 C ALA A 275 48.931 32.488 95.856 1.00 0.00 xxxx 2109 ATOM 2110 O ALA A 275 49.166 33.683 96.076 1.00 0.00 xxxx 2110 ATOM 2111 CB ALA A 275 46.482 32.054 95.636 1.00 0.00 xxxx 2111 ATOM 2112 N GLN A 276 49.604 31.510 96.454 1.00 0.00 xxxx 2112 ATOM 2113 CA GLN A 276 50.722 31.741 97.361 1.00 0.00 xxxx 2113 ATOM 2114 C GLN A 276 52.057 31.817 96.634 1.00 0.00 xxxx 2114 ATOM 2115 O GLN A 276 53.094 31.981 97.288 1.00 0.00 xxxx 2115 ATOM 2116 CB GLN A 276 50.784 30.628 98.409 1.00 0.00 xxxx 2116 ATOM 2117 CG GLN A 276 49.579 30.556 99.333 1.00 0.00 xxxx 2117 ATOM 2118 CD GLN A 276 49.603 29.331 100.233 1.00 0.00 xxxx 2118 ATOM 2119 OE1 GLN A 276 48.887 28.352 100.001 1.00 0.00 xxxx 2119 ATOM 2120 NE2 GLN A 276 50.426 29.386 101.275 1.00 0.00 xxxx 2120 ATOM 2121 N GLY A 277 52.056 31.705 95.308 1.00 0.00 xxxx 2121 ATOM 2122 CA GLY A 277 53.294 31.680 94.550 1.00 0.00 xxxx 2122 ATOM 2123 C GLY A 277 54.045 30.369 94.618 1.00 0.00 xxxx 2123 ATOM 2124 O GLY A 277 55.264 30.349 94.415 1.00 0.00 xxxx 2124 ATOM 2125 N ILE A 278 53.350 29.266 94.886 1.00 0.00 xxxx 2125 ATOM 2126 CA ILE A 278 53.963 27.956 95.076 1.00 0.00 xxxx 2126 ATOM 2127 C ILE A 278 53.561 27.072 93.905 1.00 0.00 xxxx 2127 ATOM 2128 O ILE A 278 52.384 27.034 93.527 1.00 0.00 xxxx 2128 ATOM 2129 CB ILE A 278 53.511 27.336 96.409 1.00 0.00 xxxx 2129 ATOM 2130 CG1 ILE A 278 53.891 28.251 97.577 1.00 0.00 xxxx 2130 ATOM 2131 CG2 ILE A 278 54.097 25.940 96.585 1.00 0.00 xxxx 2131 ATOM 2132 CD1 ILE A 278 53.323 27.804 98.910 1.00 0.00 xxxx 2132 ATOM 2133 N THR A 279 54.528 26.350 93.339 1.00 0.00 xxxx 2133 ATOM 2134 CA THR A 279 54.222 25.468 92.210 1.00 0.00 xxxx 2134 ATOM 2135 C THR A 279 53.522 24.206 92.708 1.00 0.00 xxxx 2135 ATOM 2136 O THR A 279 54.030 23.542 93.616 1.00 0.00 xxxx 2136 ATOM 2137 CB THR A 279 55.507 25.085 91.474 1.00 0.00 xxxx 2137 ATOM 2138 OG1 THR A 279 56.136 26.266 90.970 1.00 0.00 xxxx 2138 ATOM 2139 CG2 THR A 279 55.206 24.153 90.305 1.00 0.00 xxxx 2139 ATOM 2140 N PRO A 280 52.372 23.844 92.141 1.00 0.00 xxxx 2140 ATOM 2141 CA PRO A 280 51.693 22.611 92.562 1.00 0.00 xxxx 2141 ATOM 2142 C PRO A 280 52.570 21.376 92.401 1.00 0.00 xxxx 2142 ATOM 2143 O PRO A 280 53.312 21.237 91.426 1.00 0.00 xxxx 2143 ATOM 2144 CB PRO A 280 50.483 22.551 91.626 1.00 0.00 xxxx 2144 ATOM 2145 CG PRO A 280 50.192 23.983 91.318 1.00 0.00 xxxx 2145 ATOM 2146 CD PRO A 280 51.543 24.644 91.222 1.00 0.00 xxxx 2146 ATOM 2147 N THR A 281 52.488 20.487 93.396 1.00 0.00 xxxx 2147 ATOM 2148 CA THR A 281 53.091 19.158 93.353 1.00 0.00 xxxx 2148 ATOM 2149 C THR A 281 52.078 18.181 93.927 1.00 0.00 xxxx 2149 ATOM 2150 O THR A 281 51.140 18.577 94.621 1.00 0.00 xxxx 2150 ATOM 2151 CB THR A 281 54.352 19.067 94.218 1.00 0.00 xxxx 2151 ATOM 2152 OG1 THR A 281 53.984 19.227 95.593 1.00 0.00 xxxx 2152 ATOM 2153 CG2 THR A 281 55.373 20.140 93.839 1.00 0.00 xxxx 2153 ATOM 2154 N LYS A 282 52.285 16.887 93.664 1.00 0.00 xxxx 2154 ATOM 2155 CA LYS A 282 51.404 15.889 94.267 1.00 0.00 xxxx 2155 ATOM 2156 C LYS A 282 51.395 16.013 95.786 1.00 0.00 xxxx 2156 ATOM 2157 O LYS A 282 50.346 15.855 96.420 1.00 0.00 xxxx 2157 ATOM 2158 CB LYS A 282 51.817 14.480 93.832 1.00 0.00 xxxx 2158 ATOM 2159 CG LYS A 282 51.023 13.369 94.510 1.00 0.00 xxxx 2159 ATOM 2160 CD LYS A 282 51.461 11.990 94.042 1.00 0.00 xxxx 2160 ATOM 2161 CE LYS A 282 50.575 10.900 94.638 1.00 0.00 xxxx 2161 ATOM 2162 NZ LYS A 282 50.903 9.547 94.098 1.00 0.00 xxxx 2162 ATOM 2163 N ASP A 283 52.544 16.331 96.386 1.00 0.00 xxxx 2163 ATOM 2164 CA ASP A 283 52.605 16.451 97.839 1.00 0.00 xxxx 2164 ATOM 2165 C ASP A 283 51.787 17.636 98.342 1.00 0.00 xxxx 2165 ATOM 2166 O ASP A 283 51.107 17.529 99.369 1.00 0.00 xxxx 2166 ATOM 2167 CB ASP A 283 54.055 16.583 98.304 1.00 0.00 xxxx 2167 ATOM 2168 CG ASP A 283 54.833 15.287 98.184 1.00 0.00 xxxx 2168 ATOM 2169 OD1 ASP A 283 54.208 14.208 98.131 1.00 0.00 xxxx 2169 ATOM 2170 OD2 ASP A 283 56.081 15.351 98.155 1.00 0.00 xxxx 2170 ATOM 2171 N ASN A 284 51.834 18.777 97.647 1.00 0.00 xxxx 2171 ATOM 2172 CA ASN A 284 51.185 19.963 98.195 1.00 0.00 xxxx 2172 ATOM 2173 C ASN A 284 49.744 20.169 97.733 1.00 0.00 xxxx 2173 ATOM 2174 O ASN A 284 49.050 21.012 98.313 1.00 0.00 xxxx 2174 ATOM 2175 CB ASN A 284 52.050 21.233 98.047 1.00 0.00 xxxx 2175 ATOM 2176 CG ASN A 284 52.213 21.691 96.609 1.00 0.00 xxxx 2176 ATOM 2177 OD1 ASN A 284 51.340 21.487 95.771 1.00 0.00 xxxx 2177 ATOM 2178 ND2 ASN A 284 53.339 22.348 96.327 1.00 0.00 xxxx 2178 ATOM 2179 N ILE A 285 49.265 19.429 96.732 1.00 0.00 xxxx 2179 ATOM 2180 CA ILE A 285 47.845 19.447 96.394 1.00 0.00 xxxx 2180 ATOM 2181 C ILE A 285 47.131 18.152 96.753 1.00 0.00 xxxx 2181 ATOM 2182 O ILE A 285 45.892 18.151 96.822 1.00 0.00 xxxx 2182 ATOM 2183 CB ILE A 285 47.552 19.846 94.929 1.00 0.00 xxxx 2183 ATOM 2184 CG1 ILE A 285 47.964 18.729 93.966 1.00 0.00 xxxx 2184 ATOM 2185 CG2 ILE A 285 48.214 21.176 94.591 1.00 0.00 xxxx 2185 ATOM 2186 CD1 ILE A 285 47.381 18.877 92.565 1.00 0.00 xxxx 2186 ATOM 2187 N GLY A 286 47.853 17.057 96.966 1.00 0.00 xxxx 2187 ATOM 2188 CA GLY A 286 47.239 15.817 97.401 1.00 0.00 xxxx 2188 ATOM 2189 C GLY A 286 46.744 14.889 96.311 1.00 0.00 xxxx 2189 ATOM 2190 O GLY A 286 45.989 13.958 96.620 1.00 0.00 xxxx 2190 ATOM 2191 N TYR A 287 47.117 15.123 95.049 1.00 0.00 xxxx 2191 ATOM 2192 CA TYR A 287 46.656 14.329 93.912 1.00 0.00 xxxx 2192 ATOM 2193 C TYR A 287 47.783 14.234 92.898 1.00 0.00 xxxx 2193 ATOM 2194 O TYR A 287 48.562 15.175 92.738 1.00 0.00 xxxx 2194 ATOM 2195 CB TYR A 287 45.445 14.977 93.206 1.00 0.00 xxxx 2195 ATOM 2196 CG TYR A 287 44.247 15.146 94.110 1.00 0.00 xxxx 2196 ATOM 2197 CD1 TYR A 287 44.120 16.268 94.922 1.00 0.00 xxxx 2197 ATOM 2198 CD2 TYR A 287 43.247 14.173 94.173 1.00 0.00 xxxx 2198 ATOM 2199 CE1 TYR A 287 43.045 16.414 95.778 1.00 0.00 xxxx 2199 ATOM 2200 CE2 TYR A 287 42.169 14.310 95.020 1.00 0.00 xxxx 2200 ATOM 2201 CZ TYR A 287 42.072 15.436 95.823 1.00 0.00 xxxx 2201 ATOM 2202 OH TYR A 287 41.016 15.600 96.685 1.00 0.00 xxxx 2202 ATOM 2203 N ASP A 288 47.849 13.100 92.198 1.00 0.00 xxxx 2203 ATOM 2204 CA ASP A 288 48.789 12.962 91.092 1.00 0.00 xxxx 2204 ATOM 2205 C ASP A 288 48.519 13.995 90.009 1.00 0.00 xxxx 2205 ATOM 2206 O ASP A 288 47.367 14.248 89.636 1.00 0.00 xxxx 2206 ATOM 2207 CB ASP A 288 48.654 11.590 90.440 1.00 0.00 xxxx 2207 ATOM 2208 CG ASP A 288 49.223 10.483 91.279 1.00 0.00 xxxx 2208 ATOM 2209 OD1 ASP A 288 50.454 10.475 91.494 1.00 0.00 xxxx 2209 ATOM 2210 OD2 ASP A 288 48.442 9.600 91.691 1.00 0.00 xxxx 2210 ATOM 2211 N ILE A 289 49.601 14.562 89.485 1.00 0.00 xxxx 2211 ATOM 2212 CA ILE A 289 49.578 15.483 88.353 1.00 0.00 xxxx 2212 ATOM 2213 C ILE A 289 50.142 14.742 87.150 1.00 0.00 xxxx 2213 ATOM 2214 O ILE A 289 51.215 14.129 87.235 1.00 0.00 xxxx 2214 ATOM 2215 CB ILE A 289 50.395 16.751 88.654 1.00 0.00 xxxx 2215 ATOM 2216 CG1 ILE A 289 49.854 17.448 89.904 1.00 0.00 xxxx 2216 ATOM 2217 CG2 ILE A 289 50.393 17.699 87.452 1.00 0.00 xxxx 2217 ATOM 2218 CD1 ILE A 289 50.751 18.579 90.397 1.00 0.00 xxxx 2218 ATOM 2219 N THR A 290 49.412 14.779 86.040 1.00 0.00 xxxx 2219 ATOM 2220 CA THR A 290 49.764 14.060 84.824 1.00 0.00 xxxx 2220 ATOM 2221 C THR A 290 50.168 15.065 83.756 1.00 0.00 xxxx 2221 ATOM 2222 O THR A 290 49.539 16.124 83.623 1.00 0.00 xxxx 2222 ATOM 2223 CB THR A 290 48.550 13.264 84.336 1.00 0.00 xxxx 2223 ATOM 2224 OG1 THR A 290 48.119 12.361 85.365 1.00 0.00 xxxx 2224 ATOM 2225 CG2 THR A 290 48.887 12.467 83.098 1.00 0.00 xxxx 2225 ATOM 2226 N ASP A 291 51.224 14.740 83.002 1.00 0.00 xxxx 2226 ATOM 2227 CA ASP A 291 51.724 15.614 81.931 1.00 0.00 xxxx 2227 ATOM 2228 C ASP A 291 52.036 17.022 82.437 1.00 0.00 xxxx 2228 ATOM 2229 O ASP A 291 51.957 17.998 81.684 1.00 0.00 xxxx 2229 ATOM 2230 CB ASP A 291 50.750 15.669 80.746 1.00 0.00 xxxx 2230 ATOM 2231 CG ASP A 291 50.608 14.341 80.042 1.00 0.00 xxxx 2231 ATOM 2232 OD1 ASP A 291 51.635 13.723 79.686 1.00 0.00 xxxx 2232 ATOM 2233 OD2 ASP A 291 49.463 13.904 79.833 1.00 0.00 xxxx 2233 ATOM 2234 N GLY A 292 52.400 17.143 83.712 1.00 0.00 xxxx 2234 ATOM 2235 CA GLY A 292 52.765 18.411 84.313 1.00 0.00 xxxx 2235 ATOM 2236 C GLY A 292 51.636 19.388 84.564 1.00 0.00 xxxx 2236 ATOM 2237 O GLY A 292 51.868 20.414 85.213 1.00 0.00 xxxx 2237 ATOM 2238 N LYS A 293 50.420 19.117 84.082 1.00 0.00 xxxx 2238 ATOM 2239 CA LYS A 293 49.356 20.122 84.076 1.00 0.00 xxxx 2239 ATOM 2240 C LYS A 293 47.995 19.597 84.474 1.00 0.00 xxxx 2240 ATOM 2241 O LYS A 293 47.118 20.418 84.763 1.00 0.00 xxxx 2241 ATOM 2242 CB LYS A 293 49.212 20.750 82.682 1.00 0.00 xxxx 2242 ATOM 2243 CG LYS A 293 50.461 21.455 82.158 1.00 0.00 xxxx 2243 ATOM 2244 CD LYS A 293 50.271 21.857 80.705 1.00 0.00 xxxx 2244 ATOM 2245 CE LYS A 293 51.504 22.554 80.140 1.00 0.00 xxxx 2245 ATOM 2246 NZ LYS A 293 51.585 24.001 80.516 1.00 0.00 xxxx 2246 ATOM 2247 N TYR A 294 47.750 18.290 84.462 1.00 0.00 xxxx 2247 ATOM 2248 CA TYR A 294 46.396 17.766 84.562 1.00 0.00 xxxx 2248 ATOM 2249 C TYR A 294 46.234 16.963 85.842 1.00 0.00 xxxx 2249 ATOM 2250 O TYR A 294 47.120 16.196 86.223 1.00 0.00 xxxx 2250 ATOM 2251 CB TYR A 294 46.107 16.820 83.394 1.00 0.00 xxxx 2251 ATOM 2252 CG TYR A 294 46.133 17.445 82.024 1.00 0.00 xxxx 2252 ATOM 2253 CD1 TYR A 294 47.322 17.549 81.311 1.00 0.00 xxxx 2253 ATOM 2254 CD2 TYR A 294 44.970 17.922 81.426 1.00 0.00 xxxx 2254 ATOM 2255 CE1 TYR A 294 47.355 18.114 80.041 1.00 0.00 xxxx 2255 ATOM 2256 CE2 TYR A 294 44.989 18.493 80.157 1.00 0.00 xxxx 2256 ATOM 2257 CZ TYR A 294 46.178 18.580 79.466 1.00 0.00 xxxx 2257 ATOM 2258 OH TYR A 294 46.194 19.133 78.209 1.00 0.00 xxxx 2258 ATOM 2259 N VAL A 295 45.098 17.116 86.503 1.00 0.00 xxxx 2259 ATOM 2260 CA VAL A 295 44.716 16.234 87.600 1.00 0.00 xxxx 2260 ATOM 2261 C VAL A 295 43.472 15.475 87.175 1.00 0.00 xxxx 2261 ATOM 2262 O VAL A 295 42.414 16.086 86.951 1.00 0.00 xxxx 2262 ATOM 2263 CB VAL A 295 44.463 17.008 88.897 1.00 0.00 xxxx 2263 ATOM 2264 CG1 VAL A 295 43.877 16.067 89.959 1.00 0.00 xxxx 2264 ATOM 2265 CG2 VAL A 295 45.740 17.633 89.385 1.00 0.00 xxxx 2265 ATOM 2266 N TRP A 296 43.597 14.154 87.058 1.00 0.00 xxxx 2266 ATOM 2267 CA TRP A 296 42.499 13.286 86.651 1.00 0.00 xxxx 2267 ATOM 2268 C TRP A 296 41.963 12.562 87.875 1.00 0.00 xxxx 2268 ATOM 2269 O TRP A 296 42.720 11.879 88.579 1.00 0.00 xxxx 2269 ATOM 2270 CB TRP A 296 42.984 12.264 85.627 1.00 0.00 xxxx 2270 ATOM 2271 CG TRP A 296 43.564 12.875 84.394 1.00 0.00 xxxx 2271 ATOM 2272 CD1 TRP A 296 44.852 12.768 83.952 1.00 0.00 xxxx 2272 ATOM 2273 CD2 TRP A 296 42.868 13.664 83.428 1.00 0.00 xxxx 2273 ATOM 2274 NE1 TRP A 296 45.002 13.449 82.772 1.00 0.00 xxxx 2274 ATOM 2275 CE2 TRP A 296 43.799 14.014 82.430 1.00 0.00 xxxx 2275 ATOM 2276 CE3 TRP A 296 41.548 14.121 83.318 1.00 0.00 xxxx 2276 ATOM 2277 CZ2 TRP A 296 43.451 14.796 81.322 1.00 0.00 xxxx 2277 ATOM 2278 CZ3 TRP A 296 41.197 14.894 82.230 1.00 0.00 xxxx 2278 ATOM 2279 CH2 TRP A 296 42.143 15.230 81.242 1.00 0.00 xxxx 2279 ATOM 2280 N ILE A 297 40.669 12.705 88.116 1.00 0.00 xxxx 2280 ATOM 2281 CA ILE A 297 39.992 12.097 89.258 1.00 0.00 xxxx 2281 ATOM 2282 C ILE A 297 39.213 10.888 88.746 1.00 0.00 xxxx 2282 ATOM 2283 O ILE A 297 38.483 11.019 87.754 1.00 0.00 xxxx 2283 ATOM 2284 CB ILE A 297 39.048 13.123 89.911 1.00 0.00 xxxx 2284 ATOM 2285 CG1 ILE A 297 39.825 14.359 90.410 1.00 0.00 xxxx 2285 ATOM 2286 CG2 ILE A 297 38.234 12.494 91.020 1.00 0.00 xxxx 2286 ATOM 2287 CD1 ILE A 297 40.936 14.067 91.410 1.00 0.00 xxxx 2287 ATOM 2288 N PRO A 298 39.335 9.717 89.373 1.00 0.00 xxxx 2288 ATOM 2289 CA PRO A 298 38.673 8.511 88.848 1.00 0.00 xxxx 2289 ATOM 2290 C PRO A 298 37.153 8.600 88.852 1.00 0.00 xxxx 2290 ATOM 2291 O PRO A 298 36.541 9.254 89.701 1.00 0.00 xxxx 2291 ATOM 2292 CB PRO A 298 39.139 7.402 89.803 1.00 0.00 xxxx 2292 ATOM 2293 CG PRO A 298 40.414 7.921 90.386 1.00 0.00 xxxx 2293 ATOM 2294 CD PRO A 298 40.239 9.409 90.493 1.00 0.00 xxxx 2294 ATOM 2295 N TYR A 299 36.553 7.896 87.896 1.00 0.00 xxxx 2295 ATOM 2296 CA TYR A 299 35.127 7.600 87.859 1.00 0.00 xxxx 2296 ATOM 2297 C TYR A 299 34.886 6.243 88.512 1.00 0.00 xxxx 2297 ATOM 2298 O TYR A 299 35.783 5.406 88.587 1.00 0.00 xxxx 2298 ATOM 2299 CB TYR A 299 34.673 7.509 86.405 1.00 0.00 xxxx 2299 ATOM 2300 CG TYR A 299 34.448 8.814 85.684 1.00 0.00 xxxx 2300 ATOM 2301 CD1 TYR A 299 33.321 9.584 85.936 1.00 0.00 xxxx 2301 ATOM 2302 CD2 TYR A 299 35.339 9.257 84.695 1.00 0.00 xxxx 2302 ATOM 2303 CE1 TYR A 299 33.088 10.760 85.251 1.00 0.00 xxxx 2303 ATOM 2304 CE2 TYR A 299 35.117 10.428 84.012 1.00 0.00 xxxx 2304 ATOM 2305 CZ TYR A 299 33.974 11.176 84.286 1.00 0.00 xxxx 2305 ATOM 2306 OH TYR A 299 33.700 12.363 83.634 1.00 0.00 xxxx 2306 ATOM 2307 N LYS A 300 33.647 6.018 88.962 1.00 0.00 xxxx 2307 ATOM 2308 CA LYS A 300 33.281 4.772 89.636 1.00 0.00 xxxx 2308 ATOM 2309 C LYS A 300 31.892 4.324 89.199 1.00 0.00 xxxx 2309 ATOM 2310 O LYS A 300 30.955 5.125 89.201 1.00 0.00 xxxx 2310 ATOM 2311 CB LYS A 300 33.304 4.942 91.163 1.00 0.00 xxxx 2311 ATOM 2312 CG LYS A 300 32.995 3.686 91.943 1.00 0.00 xxxx 2312 ATOM 2313 CD LYS A 300 33.317 3.875 93.417 1.00 0.00 xxxx 2313 ATOM 2314 CE LYS A 300 33.211 2.565 94.182 1.00 0.00 xxxx 2314 ATOM 2315 NZ LYS A 300 33.711 2.702 95.580 1.00 0.00 xxxx 2315 ATOM 2316 N LYS A 301 31.750 3.047 88.847 1.00 0.00 xxxx 2316 ATOM 2317 CA LYS A 301 30.456 2.506 88.445 1.00 0.00 xxxx 2317 ATOM 2318 C LYS A 301 29.495 2.456 89.631 1.00 0.00 xxxx 2318 ATOM 2319 O LYS A 301 29.872 2.039 90.729 1.00 0.00 xxxx 2319 ATOM 2320 CB LYS A 301 30.668 1.089 87.913 1.00 0.00 xxxx 2320 ATOM 2321 CG LYS A 301 29.452 0.450 87.283 1.00 0.00 xxxx 2321 ATOM 2322 CD LYS A 301 29.731 −1.015 86.917 1.00 0.00 xxxx 2322 ATOM 2323 CE LYS A 301 30.833 −1.162 85.862 1.00 0.00 xxxx 2323 ATOM 2324 NZ LYS A 301 31.026 −2.605 85.495 1.00 0.00 xxxx 2324 ATOM 2325 N ILE A 302 28.237 2.850 89.401 1.00 0.00 xxxx 2325 ATOM 2326 CA ILE A 302 27.199 2.842 90.435 1.00 0.00 xxxx 2326 ATOM 2327 C ILE A 302 25.950 2.144 89.895 1.00 0.00 xxxx 2327 ATOM 2328 O ILE A 302 25.369 2.584 88.892 1.00 0.00 xxxx 2328 ATOM 2329 CB ILE A 302 26.836 4.266 90.901 1.00 0.00 xxxx 2329 ATOM 2330 CG1 ILE A 302 28.054 5.047 91.407 1.00 0.00 xxxx 2330 ATOM 2331 CG2 ILE A 302 25.714 4.217 91.934 1.00 0.00 xxxx 2331 ATOM 2332 CD1 ILE A 302 28.689 4.485 92.677 1.00 0.00 xxxx 2332 ATOM 2333 N THR A 303 25.510 1.093 90.584 1.00 0.00 xxxx 2333 ATOM 2334 CA THR A 303 24.195 0.508 90.335 1.00 0.00 xxxx 2334 ATOM 2335 C THR A 303 23.474 0.302 91.663 1.00 0.00 xxxx 2335 ATOM 2336 O THR A 303 23.969 0.724 92.713 1.00 0.00 xxxx 2336 ATOM 2337 CB THR A 303 24.281 −0.832 89.591 1.00 0.00 xxxx 2337 ATOM 2338 OG1 THR A 303 24.863 −1.821 90.450 1.00 0.00 xxxx 2338 ATOM 2339 CG2 THR A 303 25.111 −0.723 88.315 1.00 0.00 xxxx 2339 ATOM 2340 O LYS A 304 22.265 −1.400 95.049 1.00 0.00 xxxx 2340 ATOM 2341 N LYS A 304 22.310 −0.349 91.637 1.00 0.00 xxxx 2341 ATOM 2342 CA LYS A 304 21.616 −0.622 92.889 1.00 0.00 xxxx 2342 ATOM 2343 C LYS A 304 22.469 −1.461 93.833 1.00 0.00 xxxx 2343 ATOM 2344 CB LYS A 304 20.262 −1.290 92.628 1.00 0.00 xxxx 2344 ATOM 2345 CG LYS A 304 20.350 −2.695 92.059 1.00 0.00 xxxx 2345 ATOM 2346 CD LYS A 304 18.954 −3.279 91.841 1.00 0.00 xxxx 2346 ATOM 2347 CE LYS A 304 19.020 −4.700 91.304 1.00 0.00 xxxx 2347 ATOM 2348 NZ LYS A 304 17.663 −5.253 91.028 1.00 0.00 xxxx 2348 ATOM 2349 O ASP A 305 25.678 −2.904 96.040 1.00 0.00 xxxx 2349 ATOM 2350 N ASP A 305 23.438 −2.214 93.303 1.00 0.00 xxxx 2350 ATOM 2351 CA ASP A 305 24.251 −3.096 94.137 1.00 0.00 xxxx 2351 ATOM 2352 C ASP A 305 25.233 −2.346 95.030 1.00 0.00 xxxx 2352 ATOM 2353 CB ASP A 305 25.015 −4.096 93.267 1.00 0.00 xxxx 2353 ATOM 2354 CG ASP A 305 24.095 −5.040 92.517 1.00 0.00 xxxx 2354 ATOM 2355 OD1 ASP A 305 22.980 −5.309 93.014 1.00 0.00 xxxx 2355 ATOM 2356 OD2 ASP A 305 24.492 −5.517 91.432 1.00 0.00 xxxx 2356 ATOM 2357 O ASN A 306 27.103 1.971 95.532 1.00 0.00 xxxx 2357 ATOM 2358 N ASN A 306 25.591 −1.108 94.693 1.00 0.00 xxxx 2358 ATOM 2359 CA ASN A 306 26.605 −0.378 95.451 1.00 0.00 xxxx 2359 ATOM 2360 C ASN A 306 26.239 1.091 95.577 1.00 0.00 xxxx 2360 ATOM 2361 CB ASN A 306 28.002 −0.550 94.848 1.00 0.00 xxxx 2361 ATOM 2362 CG ASN A 306 28.157 0.154 93.506 1.00 0.00 xxxx 2362 ATOM 2363 OD1 ASN A 306 27.213 0.251 92.728 1.00 0.00 xxxx 2363 ATOM 2364 ND2 ASN A 306 29.350 0.652 93.237 1.00 0.00 xxxx 2364 ATOM 2365 N ILE A 307 24.949 1.374 95.760 1.00 0.00 xxxx 2365 ATOM 2366 CA ILE A 307 24.491 2.758 95.743 1.00 0.00 xxxx 2366 ATOM 2367 C ILE A 307 25.148 3.570 96.853 1.00 0.00 xxxx 2367 ATOM 2368 O ILE A 307 25.348 4.783 96.713 1.00 0.00 xxxx 2368 ATOM 2369 CB ILE A 307 22.947 2.803 95.773 1.00 0.00 xxxx 2369 ATOM 2370 CG1 ILE A 307 22.438 4.196 95.404 1.00 0.00 xxxx 2370 ATOM 2371 CG2 ILE A 307 22.418 2.342 97.124 1.00 0.00 xxxx 2371 ATOM 2372 CD1 ILE A 307 22.867 4.653 94.025 1.00 0.00 xxxx 2372 ATOM 2373 O SER A 308 28.067 5.083 99.317 1.00 0.00 xxxx 2373 ATOM 2374 N SER A 308 25.542 2.914 97.949 1.00 0.00 xxxx 2374 ATOM 2375 CA SER A 308 26.201 3.623 99.038 1.00 0.00 xxxx 2375 ATOM 2376 C SER A 308 27.576 4.164 98.655 1.00 0.00 xxxx 2376 ATOM 2377 CB SER A 308 26.294 2.732 100.281 1.00 0.00 xxxx 2377 ATOM 2378 OG SER A 308 27.025 1.548 100.014 1.00 0.00 xxxx 2378 ATOM 2379 O ASP A 309 30.354 6.303 96.505 1.00 0.00 xxxx 2379 ATOM 2380 N ASP A 309 28.208 3.628 97.602 1.00 0.00 xxxx 2380 ATOM 2381 CA ASP A 309 29.484 4.176 97.152 1.00 0.00 xxxx 2381 ATOM 2382 C ASP A 309 29.348 5.594 96.612 1.00 0.00 xxxx 2382 ATOM 2383 CB ASP A 309 30.119 3.293 96.076 1.00 0.00 xxxx 2383 ATOM 2384 CG ASP A 309 30.435 1.895 96.574 1.00 0.00 xxxx 2384 ATOM 2385 OD1 ASP A 309 30.291 1.646 97.790 1.00 0.00 xxxx 2385 ATOM 2386 OD2 ASP A 309 30.836 1.048 95.746 1.00 0.00 xxxx 2386 ATOM 2387 O ALA A 310 27.266 9.493 96.726 1.00 0.00 xxxx 2387 ATOM 2388 N ALA A 310 28.140 6.016 96.251 1.00 0.00 xxxx 2388 ATOM 2389 CA ALA A 310 27.910 7.386 95.816 1.00 0.00 xxxx 2389 ATOM 2390 C ALA A 310 27.485 8.298 96.957 1.00 0.00 xxxx 2390 ATOM 2391 CB ALA A 310 26.869 7.420 94.692 1.00 0.00 xxxx 2391 ATOM 2392 O ALA A 311 24.594 8.506 99.260 1.00 0.00 xxxx 2392 ATOM 2393 N ALA A 311 27.370 7.760 98.171 1.00 0.00 xxxx 2393 ATOM 2394 CA ALA A 311 26.990 8.515 99.366 1.00 0.00 xxxx 2394 ATOM 2395 C ALA A 311 25.625 9.178 99.219 1.00 0.00 xxxx 2395 ATOM 2396 CB ALA A 311 28.065 9.543 99.730 1.00 0.00 xxxx 2396 HETATM 2397 CA CA B 1 16.457 −6.247 69.477 1.00 0.00 xxxx 2397 HETATM 2398 K K C 1 8.586 −1.863 85.542 1.00 0.00 xxxx 2398 HETATM 2399 C2 GLC D 1 28.679 16.468 83.705 1.00 0.00 xxxx 2399 HETATM 2400 C3 GLC D 1 27.481 17.202 83.221 1.00 0.00 xxxx 2400 HETATM 2401 C4 GLC D 1 27.709 18.688 83.223 1.00 0.00 xxxx 2401 HETATM 2402 C5 GLC D 1 28.951 19.065 82.410 1.00 0.00 xxxx 2402 HETATM 2403 C6 GLC D 1 29.243 20.532 82.547 1.00 0.00 xxxx 2403 HETATM 2404 C1 GLC D 1 29.897 16.851 82.877 1.00 0.00 xxxx 2404 HETATM 2405 O1 GLC D 1 31.017 16.223 83.335 1.00 0.00 xxxx 2405 HETATM 2406 O2 GLC D 1 28.476 15.049 83.557 1.00 0.00 xxxx 2406 HETATM 2407 O3 GLC D 1 26.342 16.887 84.074 1.00 0.00 xxxx 2407 HETATM 2408 O4 GLC D 1 26.558 19.344 82.679 1.00 0.00 xxxx 2408 HETATM 2409 O5 GLC D 1 30.117 18.327 82.909 1.00 0.00 xxxx 2409 HETATM 2410 O6 GLC D 1 30.409 20.896 81.835 1.00 0.00 xxxx 2410 HETATM 2411 C1 EDO E 1 28.447 15.468 78.549 1.00 0.00 xxxx 2411 HETATM 2412 O1 EDO E 1 27.629 15.608 79.715 1.00 0.00 xxxx 2412 HETATM 2413 C2 EDO E 1 29.009 16.837 78.200 1.00 0.00 xxxx 2413 HETATM 2414 O2 EDO E 1 27.978 17.680 77.675 1.00 0.00 xxxx 2414 HETATM 2415 C1 EDO E 2 53.188 23.568 84.402 1.00 0.00 xxxx 2415 HETATM 2416 O1 EDO E 2 53.278 22.553 83.402 1.00 0.00 xxxx 2416 HETATM 2417 C2 EDO E 2 51.756 24.090 84.478 1.00 0.00 xxxx 2417 HETATM 2418 O2 EDO E 2 51.308 24.639 83.236 1.00 0.00 xxxx 2418 HETATM 2419 C01 ACR H 1 19.055 26.785 76.517 1.00 0.00 xxxx 2419 HETATM 2420 N02 ACR H 1 20.403 26.622 76.004 1.00 0.00 xxxx 2420 HETATM 2421 C03 ACR H 1 20.830 27.369 74.835 1.00 0.00 xxxx 2421 HETATM 2422 C04 ACR H 1 21.328 25.718 76.663 1.00 0.00 xxxx 2422 HETATM 2423 C05 ACR H 1 22.614 25.565 76.162 1.00 0.00 xxxx 2423 HETATM 2424 C06 ACR H 1 23.528 24.678 76.800 1.00 0.00 xxxx 2424 HETATM 2425 C07 ACR H 1 23.153 23.984 77.912 1.00 0.00 xxxx 2425 HETATM 2426 C08 ACR H 1 21.832 24.146 78.425 1.00 0.00 xxxx 2426 HETATM 2427 C09 ACR H 1 20.933 25.003 77.796 1.00 0.00 xxxx 2427 HETATM 2428 C10 ACR H 1 24.080 23.107 78.556 1.00 0.00 xxxx 2428 HETATM 2429 C11 ACR H 1 25.359 22.951 78.034 1.00 0.00 xxxx 2429 HETATM 2430 C12 ACR H 1 25.728 23.661 76.894 1.00 0.00 xxxx 2430 HETATM 2431 C13 ACR H 1 24.838 24.526 76.273 1.00 0.00 xxxx 2431 HETATM 2432 C14 ACR H 1 26.395 22.024 78.667 1.00 0.00 xxxx 2432 HETATM 2433 O15 ACR H 1 27.467 21.949 78.192 1.00 0.00 xxxx 2433 HETATM 2434 C16 ACR H 1 26.126 21.160 79.883 1.00 0.00 xxxx 2434 HETATM 2435 C17 ACR H 1 26.800 19.811 79.689 1.00 0.00 xxxx 2435 HETATM 2436 O HOH S 1 30.092 16.560 69.763 1.00 0.00 xxxx 2436 HETATM 2437 O HOH S 2 36.450 31.048 102.042 1.00 0.00 xxxx 2437 HETATM 2438 O HOH S 3 16.169 1.966 83.610 1.00 0.00 xxxx 2438 HETATM 2439 O HOH S 4 27.012 −3.982 66.101 1.00 0.00 xxxx 2439 HETATM 2440 O HOH S 5 27.395 35.750 89.728 1.00 0.00 xxxx 2440 HETATM 2441 O HOH S 6 35.304 11.725 88.646 1.00 0.00 xxxx 2441 HETATM 2442 O HOH S 7 34.716 3.959 68.498 1.00 0.00 xxxx 2442 HETATM 2443 O HOH S 8 16.439 12.089 65.942 1.00 0.00 xxxx 2443 HETATM 2444 O HOH S 9 6.696 12.145 83.586 1.00 0.00 xxxx 2444 HETATM 2445 O HOH S 10 14.814 −3.632 76.616 1.00 0.00 xxxx 2445 HETATM 2446 O HOH S 11 23.616 15.519 85.687 1.00 0.00 xxxx 2446 HETATM 2447 O HOH S 12 46.338 12.955 87.369 1.00 0.00 xxxx 2447 HETATM 2448 O HOH S 13 26.279 2.184 66.534 1.00 0.00 xxxx 2448 HETATM 2449 O HOH S 14 34.001 1.213 88.945 1.00 0.00 xxxx 2449 HETATM 2450 O HOH S 15 34.606 16.880 82.868 1.00 0.00 xxxx 2450 HETATM 2451 O HOH S 16 12.461 8.169 88.923 1.00 0.00 xxxx 2451 HETATM 2452 O HOH S 17 37.297 16.495 82.586 1.00 0.00 xxxx 2452 HETATM 2453 O HOH S 18 43.859 19.311 77.028 1.00 0.00 xxxx 2453 HETATM 2454 O HOH S 19 28.529 −3.638 85.001 1.00 0.00 xxxx 2454 HETATM 2455 O HOH S 20 33.875 38.445 74.722 1.00 0.00 xxxx 2455 HETATM 2456 O HOH S 21 17.882 0.880 89.534 1.00 0.00 xxxx 2456 HETATM 2457 O HOH S 22 11.808 11.066 65.996 1.00 0.00 xxxx 2457 HETATM 2458 O HOH S 23 24.159 −9.493 70.074 1.00 0.00 xxxx 2458 HETATM 2459 O HOH S 24 20.576 −0.886 89.292 1.00 0.00 xxxx 2459 HETATM 2460 O HOH S 25 29.190 18.985 97.045 1.00 0.00 xxxx 2460 HETATM 2461 O HOH S 26 26.788 39.605 80.411 1.00 0.00 xxxx 2461 HETATM 2462 O HOH S 27 24.557 18.202 85.565 1.00 0.00 xxxx 2462 HETATM 2463 O HOH S 28 35.400 13.582 82.109 1.00 0.00 xxxx 2463 HETATM 2464 O HOH S 29 44.791 21.375 70.688 1.00 0.00 xxxx 2464 HETATM 2465 O HOH S 30 6.697 10.506 76.242 1.00 0.00 xxxx 2465 HETATM 2466 O HOH S 31 51.672 12.982 77.051 1.00 0.00 xxxx 2466 HETATM 2467 O HOH S 32 56.034 19.661 97.314 1.00 0.00 xxxx 2467 HETATM 2468 O HOH S 33 29.447 38.703 87.461 1.00 0.00 xxxx 2468 HETATM 2469 O HOH S 34 31.834 40.107 87.450 1.00 0.00 xxxx 2469 HETATM 2470 O HOH S 35 26.756 8.061 76.968 1.00 0.00 xxxx 2470 HETATM 2471 O HOH S 36 24.158 −3.872 85.032 1.00 0.00 xxxx 2471 HETATM 2472 O HOH S 37 28.052 −9.997 82.594 1.00 0.00 xxxx 2472 HETATM 2473 O HOH S 38 34.765 −2.208 85.587 1.00 0.00 xxxx 2473 HETATM 2474 O HOH S 39 44.975 12.459 90.427 1.00 0.00 xxxx 2474 HETATM 2475 O HOH S 40 15.133 −2.935 64.022 1.00 0.00 xxxx 2475 HETATM 2476 O HOH S 41 8.577 16.115 72.053 1.00 0.00 xxxx 2476 HETATM 2477 O HOH S 42 7.570 15.181 85.619 1.00 0.00 xxxx 2477 HETATM 2478 O HOH S 43 26.618 25.114 89.009 1.00 0.00 xxxx 2478 HETATM 2479 O HOH S 44 15.306 11.677 90.607 1.00 0.00 xxxx 2479 HETATM 2480 O HOH S 45 31.455 11.143 69.784 1.00 0.00 xxxx 2480 HETATM 2481 O HOH S 46 14.230 −4.380 79.195 1.00 0.00 xxxx 2481 HETATM 2482 O HOH S 47 28.436 31.409 74.855 1.00 0.00 xxxx 2482 HETATM 2483 O HOH S 48 13.398 −3.445 68.777 1.00 0.00 xxxx 2483 HETATM 2484 O HOH S 49 46.833 13.403 80.483 1.00 0.00 xxxx 2484 HETATM 2485 O HOH S 50 39.393 9.798 85.489 1.00 0.00 xxxx 2485 HETATM 2486 O HOH S 51 53.217 26.247 87.539 1.00 0.00 xxxx 2486 HETATM 2487 O HOH S 52 52.319 13.823 90.231 1.00 0.00 xxxx 2487 HETATM 2488 O HOH S 53 25.425 −10.186 83.126 1.00 0.00 xxxx 2488 HETATM 2489 O HOH S 54 33.599 −1.151 87.935 1.00 0.00 xxxx 2489 HETATM 2490 O HOH S 55 35.829 −0.809 75.826 1.00 0.00 xxxx 2490 HETATM 2491 O HOH S 56 44.377 39.555 97.245 1.00 0.00 xxxx 2491 HETATM 2492 O HOH S 57 41.203 25.747 74.709 1.00 0.00 xxxx 2492 HETATM 2493 O HOH S 58 29.032 40.994 81.246 1.00 0.00 xxxx 2493 HETATM 2494 O HOH S 59 29.561 24.457 100.956 1.00 0.00 xxxx 2494 HETATM 2495 O HOH S 60 35.032 43.355 82.796 1.00 0.00 xxxx 2495 HETATM 2496 O HOH S 61 32.631 −9.718 77.045 1.00 0.00 xxxx 2496 HETATM 2497 O HOH S 62 13.214 11.510 86.158 1.00 0.00 xxxx 2497 HETATM 2498 O HOH S 63 56.614 23.565 94.666 1.00 0.00 xxxx 2498 HETATM 2499 O HOH S 64 33.119 −4.569 76.962 1.00 0.00 xxxx 2499 HETATM 2500 O HOH S 65 12.974 21.174 73.803 1.00 0.00 xxxx 2500 HETATM 2501 O HOH S 66 22.604 19.997 84.777 1.00 0.00 xxxx 2501 HETATM 2502 O HOH S 67 46.034 10.343 87.911 1.00 0.00 xxxx 2502 HETATM 2503 O HOH S 68 23.211 33.726 89.295 1.00 0.00 xxxx 2503 HETATM 2504 O HOH S 69 28.425 14.026 91.190 1.00 0.00 xxxx 2504 HETATM 2505 O HOH S 70 12.304 13.485 66.471 1.00 0.00 xxxx 2505 HETATM 2506 O HOH S 71 19.625 11.334 96.551 1.00 0.00 xxxx 2506 HETATM 2507 O HOH S 72 31.429 −5.274 84.049 1.00 0.00 xxxx 2507 HETATM 2508 O HOH S 73 57.230 26.290 94.575 1.00 0.00 xxxx 2508 HETATM 2509 O HOH S 74 30.402 8.799 68.454 1.00 0.00 xxxx 2509 HETATM 2510 O HOH S 75 42.305 41.421 80.757 1.00 0.00 xxxx 2510 HETATM 2511 O HOH S 76 31.668 −4.011 87.949 1.00 0.00 xxxx 2511 HETATM 2512 O HOH S 77 31.815 41.234 84.994 1.00 0.00 xxxx 2512 HETATM 2513 O HOH S 78 23.437 16.457 93.563 1.00 0.00 xxxx 2513 HETATM 2514 O HOH S 79 41.303 43.139 82.512 1.00 0.00 xxxx 2514 HETATM 2515 O HOH S 80 21.590 15.150 87.659 1.00 0.00 xxxx 2515 HETATM 2516 O HOH S 81 18.486 10.518 65.200 1.00 0.00 xxxx 2516 HETATM 2517 O HOH S 82 9.071 −4.275 79.356 1.00 0.00 xxxx 2517 HETATM 2518 O HOH S 83 36.449 19.498 87.421 1.00 0.00 xxxx 2518 HETATM 2519 O HOH S 84 21.050 −3.581 88.635 1.00 0.00 xxxx 2519 HETATM 2520 O HOH S 85 35.483 43.694 80.045 1.00 0.00 xxxx 2520 HETATM 2521 O HOH S 86 37.504 44.950 83.775 1.00 0.00 xxxx 2521 HETATM 2522 O HOH S 87 16.431 0.525 86.039 1.00 0.00 xxxx 2522 HETATM 2523 O HOH S 88 31.460 4.265 69.160 1.00 0.00 xxxx 2523 HETATM 2524 O HOH S 89 29.009 −10.068 85.371 1.00 0.00 xxxx 2524 HETATM 2525 O HOH S 90 13.694 13.831 68.979 1.00 0.00 xxxx 2525 HETATM 2526 O HOH S 91 28.377 38.397 89.848 1.00 0.00 xxxx 2526 HETATM 2527 O HOH S 92 48.576 19.589 76.520 1.00 0.00 xxxx 2527 HETATM 2528 O HOH S 93 39.565 14.665 76.878 1.00 0.00 xxxx 2528 HETATM 2529 O HOH S 94 47.590 40.078 97.330 1.00 0.00 xxxx 2529 HETATM 2530 O HOH S 95 32.776 43.743 84.124 1.00 0.00 xxxx 2530 HETATM 2531 O HOH S 96 43.503 9.388 88.768 1.00 0.00 xxxx 2531 HETATM 2532 O HOH S 97 36.606 31.514 104.837 1.00 0.00 xxxx 2532 HETATM 2533 O HOH S 98 23.177 34.181 79.704 1.00 0.00 xxxx 2533 HETATM 2534 O HOH S 99 49.499 25.604 101.501 1.00 0.00 xxxx 2534 HETATM 2535 O HOH S 100 47.490 39.442 91.128 1.00 0.00 xxxx 2535 HETATM 2536 O HOH S 101 26.419 −4.194 86.572 1.00 0.00 xxxx 2536 HETATM 2537 O HOH S 102 34.198 38.905 87.825 1.00 0.00 xxxx 2537 HETATM 2538 O HOH S 103 4.491 5.093 83.968 1.00 0.00 xxxx 2538 HETATM 2539 O HOH S 104 46.687 10.503 80.515 1.00 0.00 xxxx 2539 HETATM 2540 O HOH S 105 29.607 −7.424 79.355 1.00 0.00 xxxx 2540 HETATM 2541 O HOH S 106 27.866 16.980 91.747 1.00 0.00 xxxx 2541 HETATM 2542 O HOH S 107 31.275 2.036 68.201 1.00 0.00 xxxx 2542 HETATM 2543 O HOH S 108 7.908 12.189 66.781 1.00 0.00 xxxx 2543 HETATM 2544 O HOH S 109 9.363 −9.067 73.636 1.00 0.00 xxxx 2544 HETATM 2545 O HOH S 110 40.595 31.137 72.661 1.00 0.00 xxxx 2545 HETATM 2546 O HOH S 111 35.532 40.803 77.645 1.00 0.00 xxxx 2546 HETATM 2547 O HOH S 112 16.446 8.631 64.211 1.00 0.00 xxxx 2547 HETATM 2548 O HOH S 113 29.345 40.196 77.301 1.00 0.00 xxxx 2548 HETATM 2549 O HOH S 114 17.140 −3.801 86.092 1.00 0.00 xxxx 2549 HETATM 2550 O HOH S 115 31.311 −8.460 82.052 1.00 0.00 xxxx 2550 HETATM 2551 O HOH S 116 21.060 −11.983 72.146 1.00 0.00 xxxx 2551 HETATM 2552 O HOH S 117 32.758 46.230 85.726 1.00 0.00 xxxx 2552 HETATM 2553 O HOH S 118 53.994 22.636 77.590 1.00 0.00 xxxx 2553 HETATM 2554 O HOH S 119 34.245 8.721 91.171 1.00 0.00 xxxx 2554 HETATM 2555 O HOH S 120 38.082 10.310 98.438 1.00 0.00 xxxx 2555 HETATM 2556 O HOH S 121 30.850 36.982 93.600 1.00 0.00 xxxx 2556 HETATM 2557 O HOH S 122 26.285 19.723 97.088 1.00 0.00 xxxx 2557 HETATM 2558 O HOH S 123 45.716 40.764 80.927 1.00 0.00 xxxx 2558 HETATM 2559 O HOH S 124 36.475 30.550 71.465 1.00 0.00 xxxx 2559 HETATM 2560 O HOH S 125 32.694 39.932 76.320 1.00 0.00 xxxx 2560 HETATM 2561 O HOH S 126 50.009 10.367 86.104 1.00 0.00 xxxx 2561 HETATM 2562 O HOH S 127 19.479 −5.083 86.899 1.00 0.00 xxxx 2562 HETATM 2563 O HOH S 128 27.186 11.686 94.668 1.00 0.00 xxxx 2563 HETATM 2564 O HOH S 129 6.860 11.716 87.403 1.00 0.00 xxxx 2564 HETATM 2565 O HOH S 130 41.852 41.554 100.254 1.00 0.00 xxxx 2565 HETATM 2566 O HOH S 131 43.068 15.082 77.399 1.00 0.00 xxxx 2566 HETATM 2567 O HOH S 132 33.563 −10.047 74.521 1.00 0.00 xxxx 2567 HETATM 2568 O HOH S 133 37.144 9.300 92.542 1.00 0.00 xxxx 2568 HETATM 2569 O HOH S 134 54.774 26.897 78.378 1.00 0.00 xxxx 2569 HETATM 2570 O HOH S 135 15.642 9.381 61.627 1.00 0.00 xxxx 2570 HETATM 2571 O HOH S 136 34.168 11.752 97.033 1.00 0.00 xxxx 2571 HETATM 2572 O HOH S 137 19.053 −9.754 63.423 1.00 0.00 xxxx 2572 HETATM 2573 O HOH S 138 18.427 9.458 97.304 1.00 0.00 xxxx 2573 HETATM 2574 O HOH S 139 32.375 30.044 102.996 1.00 0.00 xxxx 2574 HETATM 2575 O HOH S 140 30.318 −12.055 74.888 1.00 0.00 xxxx 2575 HETATM 2576 O HOH S 141 25.415 17.615 92.333 1.00 0.00 xxxx 2576 HETATM 2577 O HOH S 142 40.031 8.276 72.106 1.00 0.00 xxxx 2577 HETATM 2578 O HOH S 143 31.155 −5.135 79.278 1.00 0.00 xxxx 2578 HETATM 2579 O HOH S 144 20.293 −13.572 84.517 1.00 0.00 xxxx 2579 HETATM 2580 O HOH S 145 47.032 42.857 82.340 1.00 0.00 xxxx 2580 HETATM 2581 O HOH S 146 30.539 27.905 103.630 1.00 0.00 xxxx 2581 HETATM 2582 O HOH S 147 26.102 −11.385 69.050 1.00 0.00 xxxx 2582 HETATM 2583 O HOH S 148 32.306 18.813 100.642 1.00 0.00 xxxx 2583 HETATM 2584 O HOH S 149 34.316 23.340 105.452 1.00 0.00 xxxx 2584 HETATM 2585 O HOH S 150 48.231 40.600 93.204 1.00 0.00 xxxx 2585 HETATM 2586 O HOH S 151 26.105 32.866 74.276 1.00 0.00 xxxx 2586 HETATM 2587 O HOH S 152 26.276 −7.076 87.052 1.00 0.00 xxxx 2587 HETATM 2588 O HOH S 153 28.787 27.403 97.004 1.00 0.00 xxxx 2588 HETATM 2589 O HOH S 154 17.129 −12.891 74.110 1.00 0.00 xxxx 2589 HETATM 2590 O HOH S 155 9.512 14.016 65.802 1.00 0.00 xxxx 2590 HETATM 2591 O HOH S 156 21.215 17.960 93.737 1.00 0.00 xxxx 2591 HETATM 2592 O HOH S 157 41.716 8.612 86.096 1.00 0.00 xxxx 2592 HETATM 2593 O HOH S 158 29.408 −12.119 70.047 1.00 0.00 xxxx 2593 HETATM 2594 O HOH S 159 25.011 −12.819 82.517 1.00 0.00 xxxx 2594 HETATM 2595 O HOH S 160 32.663 −5.811 81.679 1.00 0.00 xxxx 2595 HETATM 2596 O HOH S 161 24.880 19.576 95.065 1.00 0.00 xxxx 2596 HETATM 2597 O HOH S 162 44.355 29.891 71.184 1.00 0.00 xxxx 2597 HETATM 2598 O HOH S 163 34.518 29.416 101.548 1.00 0.00 xxxx 2598 HETATM 2599 O HOH S 164 35.180 32.267 100.121 1.00 0.00 xxxx 2599 HETATM 2600 O HOH S 165 23.399 −10.513 72.364 1.00 0.00 xxxx 2600 HETATM 2601 O HOH S 166 16.052 14.146 67.637 1.00 0.00 xxxx 2601 HETATM 2602 O HOH S 167 14.427 −6.559 82.883 1.00 0.00 xxxx 2602 HETATM 2603 O HOH S 168 13.244 −2.741 65.936 1.00 0.00 xxxx 2603 HETATM 2604 O HOH S 169 7.373 2.815 64.826 1.00 0.00 xxxx 2604 HETATM 2605 O HOH S 170 19.049 −9.891 75.701 1.00 0.00 xxxx 2605 HETATM 2606 O HOH S 171 45.770 25.436 70.089 1.00 0.00 xxxx 2606 HETATM 2607 O HOH S 172 14.520 22.711 75.198 1.00 0.00 xxxx 2607 HETATM 2608 O HOH S 173 11.837 −6.376 82.392 1.00 0.00 xxxx 2608 HETATM 2609 O HOH S 174 42.682 22.064 101.116 1.00 0.00 xxxx 2609 HETATM 2610 O HOH S 175 11.747 −5.386 79.675 1.00 0.00 xxxx 2610 HETATM 2611 O HOH S 176 51.980 18.978 79.010 1.00 0.00 xxxx 2611 HETATM 2612 O HOH S 177 28.850 −7.885 86.063 1.00 0.00 xxxx 2612 HETATM 2613 O HOH S 178 15.864 −12.993 83.108 1.00 0.00 xxxx 2613 HETATM 2614 O HOH S 179 12.312 −0.800 87.994 1.00 0.00 xxxx 2614 HETATM 2615 O HOH S 180 22.300 7.722 64.043 1.00 0.00 xxxx 2615 HETATM 2616 O HOH S 181 15.971 21.384 82.137 1.00 0.00 xxxx 2616 HETATM 2617 O HOH S 182 30.811 25.553 103.189 1.00 0.00 xxxx 2617 HETATM 2618 O HOH S 183 29.318 13.972 70.591 1.00 0.00 xxxx 2618 HETATM 2619 O HOH S 184 27.674 25.600 77.740 1.00 0.00 xxxx 2619 HETATM 2620 O HOH S 185 32.834 23.568 75.565 1.00 0.00 xxxx 2620 HETATM 2621 O HOH S 186 15.402 −10.518 83.634 1.00 0.00 xxxx 2621 HETATM 2622 O HOH S 187 29.808 39.756 83.574 1.00 0.00 xxxx 2622 HETATM 2623 O HOH S 188 33.887 31.270 104.772 1.00 0.00 xxxx 2623 HETATM 2624 O HOH S 189 20.488 −11.771 76.677 1.00 0.00 xxxx 2624 HETATM 2625 O HOH S 190 12.518 16.212 68.881 1.00 0.00 xxxx 2625 HETATM 2626 O HOH S 191 54.565 27.676 89.397 1.00 0.00 xxxx 2626 HETATM 2627 O HOH S 192 53.012 16.808 74.423 1.00 0.00 xxxx 2627 HETATM 2628 O HOH S 193 49.804 36.751 76.677 1.00 0.00 xxxx 2628 HETATM 2629 O HOH S 194 49.635 35.394 91.979 1.00 0.00 xxxx 2629 HETATM 2630 O HOH S 195 13.533 9.420 90.707 1.00 0.00 xxxx 2630 HETATM 2631 O HOH S 196 36.374 −7.847 71.968 1.00 0.00 xxxx 2631 HETATM 2632 O HOH S 197 53.604 36.390 82.878 1.00 0.00 xxxx 2632 HETATM 2633 O HOH S 198 51.181 15.057 75.617 1.00 0.00 xxxx 2633 HETATM 2634 O HOH S 199 28.232 28.892 94.774 1.00 0.00 xxxx 2634 HETATM 2635 O HOH S 200 31.413 23.690 105.190 1.00 0.00 xxxx 2635 HETATM 2636 O HOH S 201 35.263 −5.032 85.936 1.00 0.00 xxxx 2636 HETATM 2637 O HOH S 202 30.282 32.380 96.955 1.00 0.00 xxxx 2637 HETATM 2638 O HOH S 203 28.203 31.685 95.320 1.00 0.00 xxxx 2638 HETATM 2639 O HOH S 204 49.772 37.811 90.376 1.00 0.00 xxxx 2639 HETATM 2640 O HOH S 205 42.346 31.385 70.795 1.00 0.00 xxxx 2640 HETATM 2641 O HOH S 206 31.448 13.764 94.887 1.00 0.00 xxxx 2641 HETATM 2642 O HOH S 207 45.518 14.293 78.127 1.00 0.00 xxxx 2642 HETATM 2643 O HOH S 208 28.442 5.875 69.185 1.00 0.00 xxxx 2643 HETATM 2644 O HOH S 209 49.554 35.069 106.432 1.00 0.00 xxxx 2644 HETATM 2645 O HOH S 210 27.200 6.622 67.192 1.00 0.00 xxxx 2645 HETATM 2646 O HOH S 211 31.168 33.125 101.975 1.00 0.00 xxxx 2646 HETATM 2647 O HOH S 212 26.450 36.711 86.006 1.00 0.00 xxxx 2647 HETATM 2648 O HOH S 213 55.824 32.193 83.580 1.00 0.00 xxxx 2648 HETATM 2649 O HOH S 214 13.304 10.253 88.335 1.00 0.00 xxxx 2649 HETATM 2650 O HOH S 215 29.506 13.799 93.673 1.00 0.00 xxxx 2650 HETATM 2651 O HOH S 216 20.507 9.464 64.402 1.00 0.00 xxxx 2651 HETATM 2652 O HOH S 217 14.748 13.431 92.671 1.00 0.00 xxxx 2652 HETATM 2653 O HOH S 218 26.847 39.185 77.674 1.00 0.00 xxxx 2653 HETATM 2654 O HOH S 219 10.406 16.438 66.823 1.00 0.00 xxxx 2654 HETATM 2655 O HOH S 220 2.716 4.132 75.046 1.00 0.00 xxxx 2655 HETATM 2656 O HOH S 221 32.567 −2.540 89.806 1.00 0.00 xxxx 2656 HETATM 2657 O HOH S 222 48.057 8.630 88.418 1.00 0.00 xxxx 2657 HETATM 2658 O HOH S 223 38.623 36.281 77.233 1.00 0.00 xxxx 2658 HETATM 2659 O HOH S 224 5.367 0.438 69.681 1.00 0.00 xxxx 2659 HETATM 2660 O HOH S 225 55.509 29.545 79.721 1.00 0.00 xxxx 2660 HETATM 2661 O HOH S 226 45.784 11.649 77.043 1.00 0.00 xxxx 2661 HETATM 2662 O HOH S 227 46.921 22.993 98.717 1.00 0.00 xxxx 2662 HETATM 2663 O HOH S 228 14.908 −6.015 85.254 1.00 0.00 xxxx 2663 HETATM 2664 O HOH S 229 41.066 29.306 109.579 1.00 0.00 xxxx 2664 HETATM 2665 O HOH S 230 22.133 30.392 83.355 1.00 0.00 xxxx 2665 HETATM 2666 O HOH S 231 41.120 9.979 74.044 1.00 0.00 xxxx 2666 HETATM 2667 O HOH S 232 51.131 37.451 106.185 1.00 0.00 xxxx 2667 HETATM 2668 O HOH S 233 55.796 23.522 81.726 1.00 0.00 xxxx 2668 HETATM 2669 O HOH S 234 30.767 13.535 69.149 1.00 0.00 xxxx 2669 HETATM 2670 O HOH S 235 30.378 −13.413 72.516 1.00 0.00 xxxx 2670 HETATM 2671 O HOH S 236 32.947 5.925 96.446 1.00 0.00 xxxx 2671 HETATM 2672 O HOH S 237 25.500 16.096 79.243 1.00 0.00 xxxx 2672 HETATM 2673 O HOH S 238 26.802 29.069 75.273 1.00 0.00 xxxx 2673 HETATM 2674 O HOH S 239 14.192 17.963 67.834 1.00 0.00 xxxx 2674 HETATM 2675 O HOH S 240 5.905 10.203 73.585 1.00 0.00 xxxx 2675 HETATM 2676 O HOH S 241 4.513 7.800 73.072 1.00 0.00 xxxx 2676 HETATM 2677 O HOH S 242 43.660 44.657 83.268 1.00 0.00 xxxx 2677 HETATM 2678 O HOH S 243 22.969 21.825 70.556 1.00 0.00 xxxx 2678 HETATM 2679 O HOH S 244 22.901 −13.995 84.304 1.00 0.00 xxxx 2679 HETATM 2680 O HOH S 245 14.508 14.371 65.000 1.00 0.00 xxxx 2680 HETATM 2681 O HOH S 246 9.488 16.688 86.964 1.00 0.00 xxxx 2681 HETATM 2682 O HOH S 247 54.267 24.642 79.573 1.00 0.00 xxxx 2682 HETATM 2683 O HOH S 248 38.086 13.849 99.533 1.00 0.00 xxxx 2683 HETATM 2684 O HOH S 249 30.344 25.159 107.966 1.00 0.00 xxxx 2684 HETATM 2685 O HOH S 250 27.639 −1.869 64.685 1.00 0.00 xxxx 2685 HETATM 2686 O HOH S 251 37.885 24.209 105.067 1.00 0.00 xxxx 2686 HETATM 2687 O HOH S 252 24.776 −0.007 98.826 1.00 0.00 xxxx 2687 HETATM 2688 O HOH S 253 30.015 19.826 99.611 1.00 0.00 xxxx 2688 HETATM 2689 O HOH S 254 23.631 −4.295 63.805 1.00 0.00 xxxx 2689 HETATM 2690 O HOH S 255 18.259 −12.433 71.943 1.00 0.00 xxxx 2690 HETATM 2691 O HOH S 256 14.315 10.556 64.808 1.00 0.00 xxxx 2691 HETATM 2692 O HOH S 257 41.561 5.948 79.800 1.00 0.00 xxxx 2692 HETATM 2693 O HOH S 258 54.871 21.422 81.888 1.00 0.00 xxxx 2693 HETATM 2694 O HOH S 259 10.817 −9.778 75.712 1.00 0.00 xxxx 2694 HETATM 2695 O HOH S 260 47.176 25.537 68.505 1.00 0.00 xxxx 2695 HETATM 2696 O HOH S 261 25.754 −0.489 64.311 1.00 0.00 xxxx 2696 HETATM 2697 O HOH S 262 20.717 32.971 83.280 1.00 0.00 xxxx 2697 HETATM 2698 O HOH S 263 21.527 20.805 93.076 1.00 0.00 xxxx 2698 HETATM 2699 O HOH S 264 35.227 33.913 73.496 1.00 0.00 xxxx 2699 HETATM 2700 O HOH S 265 9.419 3.884 91.548 1.00 0.00 xxxx 2700 HETATM 2701 O HOH S 266 30.772 42.236 89.132 1.00 0.00 xxxx 2701 HETATM 2702 O HOH S 267 14.889 11.697 60.585 1.00 0.00 xxxx 2702 HETATM 2703 O HOH S 268 16.782 −10.334 62.350 1.00 0.00 xxxx 2703 HETATM 2704 O HOH S 269 10.923 −4.229 70.024 1.00 0.00 xxxx 2704 HETATM 2705 O HOH S 270 18.813 20.066 83.551 1.00 0.00 xxxx 2705 HETATM 2706 O HOH S 271 30.048 2.118 100.339 1.00 0.00 xxxx 2706 HETATM 2707 O HOH S 272 8.909 −5.707 70.349 1.00 0.00 xxxx 2707 HETATM 2708 O HOH S 273 38.277 9.852 70.341 1.00 0.00 xxxx 2708 HETATM 2709 O HOH S 274 17.404 17.026 87.678 1.00 0.00 xxxx 2709 HETATM 2710 O HOH S 275 2.083 0.874 81.599 1.00 0.00 xxxx 2710 HETATM 2711 O HOH S 276 40.573 25.786 107.080 1.00 0.00 xxxx 2711 HETATM 2712 O HOH S 277 47.238 18.686 100.507 1.00 0.00 xxxx 2712 HETATM 2713 O HOH S 278 45.356 30.895 104.313 1.00 0.00 xxxx 2713 HETATM 2714 O HOH S 279 37.886 0.890 74.951 1.00 0.00 xxxx 2714 HETATM 2715 O HOH S 280 44.882 32.449 71.587 1.00 0.00 xxxx 2715 HETATM 2716 O HOH S 281 45.071 19.230 101.060 1.00 0.00 xxxx 2716 HETATM 2717 O HOH S 282 53.338 21.767 88.706 1.00 0.00 xxxx 2717 HETATM 2718 O HOH S 283 38.872 12.899 78.989 1.00 0.00 xxxx 2718 HETATM 2719 O HOH S 284 50.214 34.572 75.391 1.00 0.00 xxxx 2719 HETATM 2720 O HOH S 285 9.787 22.391 75.366 1.00 0.00 xxxx 2720 HETATM 2721 O HOH S 286 25.330 34.970 91.174 1.00 0.00 xxxx 2721 HETATM 2722 O HOH S 287 19.025 22.704 75.489 1.00 0.00 xxxx 2722 HETATM 2723 O HOH S 288 6.732 14.329 70.989 1.00 0.00 xxxx 2723 HETATM 2724 O HOH S 289 28.593 23.713 71.566 1.00 0.00 xxxx 2724 HETATM 2725 O HOH S 290 48.417 10.687 76.682 1.00 0.00 xxxx 2725 HETATM 2726 O HOH S 291 9.233 23.335 72.944 1.00 0.00 xxxx 2726 HETATM 2727 O HOH S 292 19.769 −1.136 96.415 1.00 0.00 xxxx 2727 HETATM 2728 O HOH S 293 15.597 23.489 79.366 1.00 0.00 xxxx 2728 HETATM 2729 O HOH S 294 48.418 12.805 75.957 1.00 0.00 xxxx 2729 HETATM 2730 O HOH S 295 24.690 36.388 80.735 1.00 0.00 xxxx 2730 HETATM 2731 O HOH S 296 3.277 6.734 67.960 1.00 0.00 xxxx 2731 HETATM 2732 O HOH S 297 33.665 24.109 72.624 1.00 0.00 xxxx 2732 HETATM 2733 O HOH S 298 22.977 21.117 82.694 1.00 0.00 xxxx 2733 HETATM 2734 O HOH S 299 29.752 −7.071 68.645 1.00 0.00 xxxx 2734 HETATM 2735 O HOH S 300 6.795 14.005 67.913 1.00 0.00 xxxx 2735 HETATM 2736 O HOH S 301 28.876 7.221 65.323 1.00 0.00 xxxx 2736 HETATM 2737 O HOH S 302 54.121 19.945 78.093 1.00 0.00 xxxx 2737 HETATM 2738 O HOH S 303 28.461 −1.344 90.238 1.00 0.00 xxxx 2738 HETATM 2739 O HOH S 304 32.077 0.296 91.320 1.00 0.00 xxxx 2739 HETATM 2740 O HOH S 305 52.762 33.840 89.496 1.00 0.00 xxxx 2740 HETATM 2741 O HOH S 306 33.055 24.497 109.572 1.00 0.00 xxxx 2741 HETATM 2742 O HOH S 307 17.403 7.927 60.363 1.00 0.00 xxxx 2742 HETATM 2743 O HOH S 308 43.466 33.878 102.677 1.00 0.00 xxxx 2743 HETATM 2744 O HOH S 309 12.277 17.804 70.661 1.00 0.00 xxxx 2744 HETATM 2745 O HOH S 310 11.041 11.796 89.974 1.00 0.00 xxxx 2745 HETATM 2746 O HOH S 311 23.651 14.294 65.562 1.00 0.00 xxxx 2746 HETATM 2747 O HOH S 312 42.026 45.298 94.042 1.00 0.00 xxxx 2747 HETATM 2748 O HOH S 313 22.517 16.293 65.454 1.00 0.00 xxxx 2748 HETATM 2749 O HOH S 314 22.627 12.480 64.518 1.00 0.00 xxxx 2749 HETATM 2750 O HOH S 315 2.884 8.870 71.069 1.00 0.00 xxxx 2750 HETATM 2751 O HOH S 316 33.745 16.834 85.547 1.00 0.00 xxxx 2751 HETATM 2752 O HOH S 317 22.276 −5.729 85.346 1.00 0.00 xxxx 2752 HETATM 2753 O HOH S 318 17.902 8.547 58.415 1.00 0.00 xxxx 2753 HETATM 2754 O HOH S 319 37.913 34.004 75.956 1.00 0.00 xxxx 2754 HETATM 2755 O HOH S 320 4.531 12.700 72.802 1.00 0.00 xxxx 2755 HETATM 2756 O HOH S 321 24.012 −0.883 62.835 1.00 0.00 xxxx 2756 HETATM 2757 O HOH S 322 25.236 −11.299 74.409 1.00 0.00 xxxx 2757 HETATM 2758 O HOH S 323 16.111 −2.210 88.800 1.00 0.00 xxxx 2758 HETATM 2759 O HOH S 324 37.659 −1.206 71.051 1.00 0.00 xxxx 2759 HETATM 2760 O HOH S 325 37.666 −6.192 71.121 1.00 0.00 xxxx 2760 HETATM 2761 O HOH S 326 28.307 3.226 66.321 1.00 0.00 xxxx 2761 HETATM 2762 O HOH S 327 18.264 17.811 65.553 1.00 0.00 xxxx 2762 HETATM 2763 O HOH S 328 32.832 36.516 97.649 1.00 0.00 xxxx 2763 HETATM 2764 O HOH S 329 37.812 34.108 72.992 1.00 0.00 xxxx 2764 HETATM 2765 O HOH S 330 31.618 −1.175 95.798 1.00 0.00 xxxx 2765 HETATM 2766 O HOH S 331 34.949 −3.372 78.898 1.00 0.00 xxxx 2766 HETATM 2767 O HOH S 332 23.906 −12.954 76.241 1.00 0.00 xxxx 2767 HETATM 2768 O HOH S 333 36.425 4.098 70.822 1.00 0.00 xxxx 2768 HETATM 2769 O HOH S 334 39.250 45.244 81.350 1.00 0.00 xxxx 2769 HETATM 2770 O HOH S 335 4.762 13.877 66.822 1.00 0.00 xxxx 2770 HETATM 2771 O HOH S 336 28.360 33.885 93.919 1.00 0.00 xxxx 2771 HETATM 2772 O HOH S 337 37.026 −2.278 82.988 1.00 0.00 xxxx 2772 HETATM 2773 O HOH S 339 52.387 24.552 100.326 1.00 0.00 xxxx 2773 HETATM 2774 O HOH S 340 23.731 19.281 92.922 1.00 0.00 xxxx 2774 HETATM 2775 O HOH S 341 22.622 29.993 86.246 1.00 0.00 xxxx 2775 HETATM 2776 O HOH S 342 47.903 18.185 70.488 1.00 0.00 xxxx 2776 HETATM 2777 O HOH S 343 41.398 34.777 102.884 1.00 0.00 xxxx 2777 HETATM 2778 O HOH S 344 48.646 39.218 75.315 1.00 0.00 xxxx 2778 HETATM 2779 O HOH S 345 38.330 15.569 80.280 1.00 0.00 xxxx 2779 HETATM 2780 O HOH S 346 31.644 34.806 96.101 1.00 0.00 xxxx 2780 HETATM 2781 O HOH S 347 47.364 33.541 103.953 1.00 0.00 xxxx 2781 HETATM 2782 O HOH S 348 44.632 14.267 99.126 1.00 0.00 xxxx 2782 HETATM 2783 O HOH S 349 49.644 35.980 94.514 1.00 0.00 xxxx 2783 HETATM 2784 O HOH S 350 21.713 24.372 91.316 1.00 0.00 xxxx 2784 HETATM 2785 O HOH S 351 52.309 31.191 91.054 1.00 0.00 xxxx 2785 HETATM 2786 O HOH S 352 22.952 34.465 76.990 1.00 0.00 xxxx 2786 HETATM 2787 O HOH S 353 1.535 7.911 68.662 1.00 0.00 xxxx 2787 HETATM 2788 O HOH S 354 42.120 12.888 78.426 1.00 0.00 xxxx 2788 HETATM 2789 O HOH S 355 23.184 −11.886 67.081 1.00 0.00 xxxx 2789 HETATM 2790 O HOH S 356 28.553 29.065 101.938 1.00 0.00 xxxx 2790 HETATM 2791 O HOH S 357 41.272 12.381 76.436 1.00 0.00 xxxx 2791 HETATM 2792 O HOH S 358 19.489 19.564 69.735 1.00 0.00 xxxx 2792 HETATM 2793 O HOH S 359 46.136 39.282 76.126 1.00 0.00 xxxx 2793 HETATM 2794 O HOH S 360 15.145 9.336 99.422 1.00 0.00 xxxx 2794 HETATM 2795 O HOH S 361 22.838 23.616 97.095 1.00 0.00 xxxx 2795 HETATM 2796 O HOH S 362 9.603 13.336 89.036 1.00 0.00 xxxx 2796 HETATM 2797 O HOH S 363 26.386 −2.108 62.392 1.00 0.00 xxxx 2797 HETATM 2798 O HOH S 364 52.011 37.819 77.771 1.00 0.00 xxxx 2798 HETATM 2799 O HOH S 365 28.168 8.938 63.919 1.00 0.00 xxxx 2799 HETATM 2800 O HOH S 366 27.589 39.294 85.068 1.00 0.00 xxxx 2800 HETATM 2801 O HOH S 367 27.687 −12.163 86.695 1.00 0.00 xxxx 2801 HETATM 2802 O HOH S 368 44.266 8.368 83.648 1.00 0.00 xxxx 2802 HETATM 2803 O HOH S 369 46.173 42.782 86.952 1.00 0.00 xxxx 2803 HETATM 2804 O HOH S 370 14.140 12.958 88.666 1.00 0.00 xxxx 2804 HETATM 2805 O HOH S 371 34.823 19.732 100.091 1.00 0.00 xxxx 2805 HETATM 2806 O HOH S 372 46.908 9.147 83.618 1.00 0.00 xxxx 2806 HETATM 2807 O HOH S 373 24.142 29.305 94.702 1.00 0.00 xxxx 2807 HETATM 2808 O HOH S 374 18.119 −1.328 89.006 1.00 0.00 xxxx 2808 HETATM 2809 O HOH S 375 33.026 38.391 92.683 1.00 0.00 xxxx 2809 HETATM 2810 O HOH S 376 58.201 22.385 92.378 1.00 0.00 xxxx 2810 HETATM 2811 O HOH S 377 54.105 29.892 90.670 1.00 0.00 xxxx 2811 HETATM 2812 O HOH S 378 34.565 8.799 95.893 1.00 0.00 xxxx 2812 HETATM 2813 O HOH S 379 27.908 0.262 61.279 1.00 0.00 xxxx 2813 HETATM 2814 O HOH S 380 19.941 22.488 82.984 1.00 0.00 xxxx 2814 HETATM 2815 O HOH S 381 29.525 −1.794 97.959 1.00 0.00 xxxx 2815 HETATM 2816 O HOH S 382 49.648 29.585 104.557 1.00 0.00 xxxx 2816 HETATM 2817 O HOH S 383 35.408 8.346 93.778 1.00 0.00 xxxx 2817 HETATM 2818 O HOH S 384 52.470 22.521 101.253 1.00 0.00 xxxx 2818 HETATM 2819 O HOH S 385 26.897 −3.606 89.300 1.00 0.00 xxxx 2819 HETATM 2820 O HOH S 386 47.051 43.266 84.658 1.00 0.00 xxxx 2820 HETATM 2821 O HOH S 387 27.492 −1.155 98.711 1.00 0.00 xxxx 2821 HETATM 2822 O HOH S 388 50.334 39.736 96.998 1.00 0.00 xxxx 2822 HETATM 2823 O HOH S 389 53.977 16.042 91.468 1.00 0.00 xxxx 2823 HETATM 2824 O HOH S 390 55.332 22.862 98.469 1.00 0.00 xxxx 2824 HETATM 2825 O HOH S 391 55.356 15.678 95.126 1.00 0.00 xxxx 2825 HETATM 2826 O HOH S 392 29.452 26.421 74.947 1.00 0.00 xxxx 2826

EXAMPLE 13 Robust, Thermostable, Reagentless, Fluorescently Responsive Glucose Biosensors

We report the construction of a robust, thermostable, reagentless, fluorescently responsive glucose biosensor and its variants derived from T. thermosaccharolyticum (ttGGBP). These proteins are useful for high-precision chemometric measurements that span the entire clinical and industrial glucose concentration range, using fluorescence ratiometry measured with straightforward, inexpensive instrumentation.

Thermostable homologs of the E. coli Glucose-galactose binding protein (ecGGBP) were identified using a bioinformatics search strategy that applied a structure-based sequence filter to identify the subset of sequences that retain the original function within the larger collection of aligned sequence homologs. The homologs of interest appeared at sequence identities below 60% of the ecGGBP probe an unusual and surprising discovery. At this level, overall identities are weak predictors of biological function, application of the structure-based filter therefore was essential for accurate identification. The glucose-binding properties of the predicted hits were tested experimentally by constructing synthetic genes optimized for heterologous protein expression in E. coli and determining the glucose-binding properties of the expressed proteins. This search resulted in the identification of a homolog from Thermoanaerobacter thermosaccharolyticum (ttGGBP) as a suitable candidate for glucose sensor engineering.

Endosterically placed Acrylodan and Badan fluorescent conjugates were found to be highly effective ratiometric glucose sensors. A series of additional mutations were introduced to manipulate glucose affinities. Variants spanning four orders of magnitude (0.1-100 mM) were identified. Within these, a subset of mutants covers the entire pathophysiological glucose concentration range with responses that remain within 90% of the maximally achievable precision.

The ttGGBP-based FRSs can be immobilized site-specifically on magnetic beads or other solid or semi-solid substrates without affecting protein stability, fluorescence responses, or glucose affinities. They can be dried, and aged aggressively (incubation at 50° C. for 7 days or more, e g mimicking and/or exceeding environmental conditions in the field, storage or shipping) without adversely affecting sensing performance

Reagentless, fluorescently responsive sensors present a number of advantages over enzyme-based biosensors, including self-calibration, elimination of chemical transformations and multiple substrates, which together lead to simple sample-handling fluidic circuitry and rapid response times. FRSs can be used for one-time, episodic, and continuous monitoring measurements. Additionally, the use of robust engineered glucose sensors based on thermophilic proteins is likely to simplify manufacturing and distribution processes. Combination of mutant glucose sensors reported here into multiplexed arrays or composites determine glucose concentrations from hypoglycemic to the hyperosmolar hyperglycemic state samples with high precision in one measurement. Such systems have significant potential for the development of next-generation high-accuracy, wide dynamic range sensing applications in continuous monitoring, point-of-care, or wearable systems.

The Following Materials and Methods were Used to Generate the Data Described Herein.

Bioinformatic searches. Annotated genomic and plasmid sequences of 4592 prokaryotes were downloaded from the National Center of Biotechnology Information (ftp://ftp.ncbi.nih.gov/genomes/Bacteria/all.gbk.tar.gz), together with annotations recording prokaryotic lifestyles (../ProkaryotesOrganismInfo.txt). We developed the ‘ProteinHunter’ program to provide an interface and methods for organizing, querying, and analyzing these genomic sequences as well as protein structures. ProteinHunter comprises a graphical user interface, set of computer scripts, and a parallel computing environment. Together these set up the calculations, manage the flow of information and execution in each of the calculation phases, control other programs that carry out specific calculations such as BLAST and ClustalW, and visualize the results. The protein sequence for the E. coli glucose-galactose binding protein (ecGGBP) was extracted from the protein structure file 2gbp (Vyas et al. 1988 Science, 242, 1290-5), and used as the seed sequence for a uni-directional BLAST search of the downloaded prokaryotes. Pairwise BLAST alignment were selected in ProteinHunter as hits if these contained 25% or identical residues, and if the alignment covered at least 70% of the probe and target sequences. The BLAST hits identified in ProteinHunter were aligned using ClustalW (Chenna et al. 2003 Nucleic Acids Res, 31, 3497-500). A structure-based sequence filter was used to accurately distinguish glucose-binding protein from other functions within the hits. A 10-residue, non-contiguous sequence comprising the primary complementary surface (PCS) between the protein and the bound glucose in the 2gbp structure (FIG. 1A-C) was identified using ProteinHunter. PCS residues were selected as members of the PCS if the calculated distance between any of their atoms and any glucose atom was less than 5 Å, and the distances between their backbone C_(α) and any atom in glucose was greater than that of their C_(β) atom and any atom in glucose. Secondary shell residues that do not form hydrogen bonds or van der Waals contacts were removed by inspection from the resulting set. Using the overall ClustalW alignments, the subset of PCS residues were identified within each homolog and aligned. For each homolog, the number of PCS mutations relative to the ecGGBP PCS (Hamming distance, Hpcs) was counted. A H_(PCS)=0 value means that the PCS sequence is identical to that of eCGGBP; homologs with this H_(PCS) value were inferred to be glucose-binding proteins. The PCS sequences were displayed sorted by their H_(PCS) values, and within each H_(PCS) value sorted by their fraction identical residues, indicating the replicon within which they reside (chromosome or plasmid), whether this replicon contains paralogs, and the temperature tolerance (hyperthermophile, thermophile, mesophile, psychrophile, unknown), their Gram stain classification (if known), and the percentage genomic AT content. Duplicate hits were removed automatically from this list if the organism name (genus and species), fractional identity and paralogs were the same. From this list unique hyper(thermophilic) ecGGBP homologs with H_(PCS)=0 were readily identified by inspection.

Gene synthesis and mutagenesis. The amino acid sequences for the GGBP homologs identified in the bioinformatic search (see above) were extracted from the ClustalW alignment file and edited further to construct a mature polypeptide with a single cysteine that replaces the equivalent of W183 in ecGGBP for site-specific labeling with Acrylodan, using AaEditor, an in-house program developed to manipulate protein sequences. The putative leader peptide that mediates anchoring of the periplasmic-binding protein on the outside of the membrane (Gram positive bacteria) or directs secretion into the periplasm (Gram negative bacteria) was deleted by examining the multiple sequence alignment and removing the sequences N-terminal to the start of the mature ecGGBP amino acid sequence. The residue equivalent to W183 in the ecGGBP sequence was mutated to cysteine; all other cysteines were changed to alanine. A hexahistidine tag was placed behind a GGS linker at the C-terminus of the mature protein to enable metal-mediated affinity purification (Hengen 1995 Methods Enzymol, 210, 129-192). The final amino acid sequence was back-translated into a DNA sequence encoding the open reading frame (ORF), which was placed in a construct behind an efficient Shine-Dalgarno ribosome-binding site, and flanked by a T7 promoter and terminator at the 5′ and 3′ ends respectively, using the GeneFab program (Cox et al. 2007 Protein Sci, 16, 379-90). The resulting ORF sequence was optimized in context by OrfOpt or OrfMorph programs designed to predict highly expressed mRNA sequences in E. coli. The resulting DNA sequences were synthesized by oligonucleotide assembly and cloned into pUC57 by GeneWiz, Inc. (South Plainfield, N.J.). Subsequent single and multiple point mutations were constructed by preparing mutant sequences of the synthetic ORF sequences using GfMutagenesis, an in-house program that introduces point mutations into an ORF using the most prevalent codon in E. coli for an amino acid, followed by total gene synthesis.

Synthetic gene optimization. The OrfOpt and OrfMorph programs use stochastic optimization algorithms that alter choose different codons within an ORF without altering the amino acid sequence to optimize a target function designed to identify mRNA sequences that express proteins at high levels in E. coli. The OrfOpt simultaneously imposes AU-rich nucleotide composition at the 5′ and 3′ ends of the ORF, low RNA secondary structure content and favorable codon usage (Allert et al. 2010 J Mol Biol, 402, 905-18). The OrfMorph program reproduces the pattern of codon usage and RNA secondary observed in the parent genome of a protein, but using E. coli codon preferences and nucleotide composition.

Codon usage is calculated using the codon adaptation index (CAI), as described for OrfOpt, using codon frequency tables calculated for the genome under examination. The mean CAI value for a genome, μ_(c), and its standard deviation, σ_(c), are calculated over all the codons in a genome. A codon usage score, c, is calculated for each codon in an open reading frame (ORF) by averaging the CAI over a 9-codon window, centered on the codon for which this score is calculated. A normalized codon usage score, z_(c), is calculated for each codon as the Z-score: z_(c)=(c−μ_(c))/Σ_(c). A plot of z_(c) along an ORF establishes the codon usage pattern of that ORF. Rare codons (z_(c)<0) are hypothesized to slow down the elongation rate of ribosome translation, introducing “pause” sites at extremes. Such pause sites are hypothesized to direct the kinetics of co-translational protein folding, allowing a newly synthesized segment to fold before more protein is made. An RNA secondary structure score, s, is determined for each nucleotide by summing its participation in all possible hairpins that can form in its vicinity (settings: minimum stem duplex length, 4 basepairs; maximum loop length, 30 bases; vicinity length, 100 bases), as described for OrfOpt. The average secondary structure energy, μ_(s), and its standard deviation, σ_(s), are calculated over all the nucleotides in a genome. A normalized secondary structure energy score, z_(s), is calculated for each codon as the Z-score: z_(s)=(s−μ_(s))/σ_(s). A plot of z_(s) along an ORF establishes the secondary structure pattern of that ORF. Regions of above-average secondary structure (z_(s)>0) are hypothesized to slow down the elongation rate of ribosome translation, introducing “pause” sites at extremes. As with CAI-mediated pause sites, secondary structure-driven pause sites are hypothesized to direct the kinetics of co-translational protein folding. To imitate these patterns for heterologous expression of an ORF in E. coli, first the z_(c) and z_(s) scores are calculated using the parent organism codon table, μ_(c), σ_(c), μ_(s), and σ_(s) values. Second, a stochastic search algorithm is used that randomly chooses between degenerate codons to construct trial mRNA nucleotide sequences, calculating z_(c) and z_(s) scores for each trial sequence, but using the E. coli codon table, and E. coli μ _(c), σ_(c), μ_(s), and σ_(s) values. For each trial sequence, the absolute differences between the E. coli trial scores, and the wild-type scores are summed over the entire ORF. The OrfMorph program searches for a minimum of these differences. The stochastic search algorithm operates by first choosing a codon position, second choosing a degenerate codon within the allowed codons at that position. If the choice results in an improved score, the sequence is kept, otherwise it is rejected. After a position has been selected, it is removed from the pool of allowed positions, and the next is chosen from the remained. A “sweep” is completed, when all the codons in the sequence have been examined. The algorithm terminates, when two successive sweeps do not yield further improvements in the score. The resulting RNA nucleotide sequence then has codon usage patterns and secondary structure patterns that closely match those of the wild-type mRNA sequence in its parental genomic context. The hypothesis is that such matching improves production of soluble protein by mimicking co-translation folding contributions that minimize mis-folded protein intermediate aggregation.

Protein expression, purification, and fluorescent conjugate preparation. Plasmids carrying the expression constructs (see above) were transformed into KRX competent cells (Promega), and grown overnight at 37° C. on LB agar plates (100 mg/mL ampicillin). A single colony was picked and grown overnight at 37° C. in Terrific Broth (TB; Research Products International). The overnight cultures were diluted 1:20 in 500 mL TB (100 mg/mL ampicillin, 1 mM CaCl₂), grown to an optical density of A₆₀₀=0.5 at 37° C. in vigorously aerated shaker flasks, induced by the addition of 2.5 mL rhamnose (20% w/v), and grown for a further 3-4 hrs. The cells were harvested by centrifugation (5,000 rpm, 10 min). After decanting the supernatant, the cell pellets were stored −80° C. The cell pellets were thawed, resuspended in 8 mL binding buffer (10 mM imadozole, 20 mM MOPS, 500 mM NaCl, 1 mM CaCl₂, pH 7.8). Following resuspension, 3 mL of BugBuster HT (EMD Millipore) was added. After incubation (20 mins, 25° C.), the cells were lysed on ice by sonication (2 minutes of one-second on/off pulses, 20-30% power). A clarified lysate was prepared by centrifugation (15,000 rpm, 20 min, 4° C.) from which recombinant protein was purified by batch immobilized metal affinity chromatography (IMAC). Resuspended IMAC agarose beads (5 mL; Sigma-Aldrich, P6611) were added to the lysate. After incubation at 4° C. in a Mini LabRoller (Labnet International) for 1 hr, the beads were washed at least five times with binding buffer. The immobilized protein beads were resuspended in labeling buffer (20 mM MOPS, 100 mM NaCl, 1 mM CaCl₂, pH 6.9) and labeled overnight (4° C., rotating end-over-end) with a thiol-reactive fluorophore (5-fold stoichiometric excess over protein). Following two rinses with labeling buffer to remove unincorporated label, the proteins were eluted from the beads. To elute labeled protein from the IMAC beads, 6 mL of elution buffer (400 mM imidazole, 500 mM NaCl, 1 mM CaCl₂, 20 mM MOPS, pH 7.8) was added, incubated for 30 min (4° C., rotating end-over-end), and the beads removed by centrifugation. Following dialysis of the eluate against three changes of assay buffer (20 mM MOPS, 20 mM KCl, 1 mM CaCl₂, pH 7.4), using 10 kDa semi-perimeable membrane (Snakeskin tubing, Thermo Scientific), the fluorescent conjugates were concentrated in a 10 kDa cutoff spin concentrator (Vivaspin, GE Healthcare). Protein purity was assessed by SDS/PAGE. Protein concentrations were determined by (Nanodrop1000) at 280 nm (using extinction coefficients calculated from their sequence(Gill and von Hippel 1989 Anal Biochem, 182, 319-26; Artimo et al. 2012 Nucleic Acids Res, 40, W597-603), or at the fluorophore absorbance peak (Acrylodan, 391 nm and Badan, 387 nm).

Determination of temperature- and ligand-dependent fluorescence landscapes. 12-, 24-, or 48-point logarithmic titration series were prepared on a Tecan Freedom liquid-handling robot, using an in-house program, ‘TitrationPlate’, that compiles an abstract description of a multi-component titration series into machine instructions for operating the robot. Glucose concentrations were varied from 0-1.7 M in 20 mM KCl, 20 mM MOPS (pH 7.4) supplemented with either 1 mM EGTA or 1 mM CaCl₂. Temperature-dependent fluorescence emission intensities of 20 μL aliquots, each containing 10 μM protein, were measured in 384-well microtiter plates in a LightCycler 480 II (Roche) using excitation and emission wavelengths available for this instrument that most closely matched the optical characteristics of the fluorescent conjugate. Temperatures were advanced in 1K steps. At each temperature, data was collected at 1-second intervals for 60 seconds at which point the signal had relaxed to a steady value associated with the new temperature. Under these experimental photobleaching was not observed. The in-house program ‘TitrationMeltPlate’ was used to convert these observations into time-independent datasets that record fluorescence as a function of temperature for each well and associate wells with their concentration of titrant and additive. Management tools were developed to maintain a database of titrations and their analyses.

Determination of emission intensity spectra. Ligand- and wavelength-dependent emission intensities were recorded on a Nanodrop3300 (Thermo Scientific) at room temperature. Using the LED closest to the optimal excitation wavelength of the fluorophore (UV, 365 nm; blue, 470 nm; ‘white’, 460-550 nm).

Ratiometric analysis of glucose binding. Isothermal glucose titrations were extracted from the fluorescent landscape or emission spectra datasets obtained as described above. Monochromatic emission intensities I_(λ) (these intensities correspond to a bandpass intensity, recorded either with a physical filter in the case of the Roche LightCycler, or by integrating in the interval λ-δ, λ+δ in the case of an emission spectrum), were fit to

I _(λ)=^(apo)β_(λ)(1− y _(true))+^(sat)β_(λ) y _(true)   I

where ^(apo)β_(λ) and ^(sat)β_(λ) are the fluorescence baselines associated with the ligand-free and ligand-bound states of the protein, respectively, and y _(true) the fractional saturation of the protein.(Layton and Hellinga 2010 Biochemistry, 49, 10831-41.) Baseline functions can be constant, linear, or a second-order polynomial. For the ligand- and temperature-dependent fluorescence landscapes, we use a constant value for ^(apo)β_(x), but ^(sat)β_(x) is described by a linear dependence on glucose concentration, [L]:

^(sat)β_(x)=a_(x) +b _(x)[L]  2

For a single glucose-binding site, the fractional saturation is given by

$\begin{matrix} {\overset{\_}{y} = \frac{\lbrack L\rbrack}{\lbrack L\rbrack + K_{d}}} & 3 \end{matrix}$

where [L] is the ligand (glucose) concentration and K_(d) the dissociation constant, ^(true)K_(d) for y _(true).

A dichromatic, ratiometric signal is defined as the ratio of the intensities at two independent wavelengths, λ₁ and λ₂

R _(1,2) =I _(λ1) /I _(λ2)   4

This signal removes wavelength-independent emission intensity attenuation effects due to variations in conjugate concentration, photobleaching, fluctuations in excitation source intensities, and detection efficiency.(Demchenko 2010 J Fluoresc, 20, 1099-128; Demchenko 2014 Journal of Molecular Structure, 1077, 51-67) It is a key aspect for high-precision sensing using the reagentless fluorescently-responsive sensors described here. The ratiometric signal also can be fit to a binding isotherm:

R _(1,2)=^(apo)β_(R)(1− y _(R))+^(sat)β_(R) y _(R)   5

where ^(apo)β_(R) and ^(sat)β_(R) are the baselines, and y _(R) the apparent fractional saturation of the protein (with ^(app)K_(d)). In general, ^(true)K_(d)≠^(app)K_(d); if both baselines are constant, a simple relationship can be derived relating ^(app)K_(d) to ^(true)K_(d):(Grimley et al. 2013 J Neurosci, 33, 16297-309)

$\begin{matrix} {{{}_{}^{}{}_{}^{}} = {{{}_{}^{}{}_{}^{}}\frac{{}_{}^{}{}_{\lambda\; 2}^{}}{{}_{}^{}{}_{\lambda\; 2}^{}}}} & 6 \end{matrix}$

where ^(apo)I_(λ2) and ^(sat)I_(λ2) are the emission intensities of the monochromatic signal at wavelength λ₂ of the ligand-free and ligand-bound protein, respectively.

The fractional error in the chemometric concentration measurement, depends on the first derivative of the binding isotherm as follows (Marvin et al. 1997 Proc Natl Acad Sci USA, 94, 4366-71):

$\begin{matrix} {\frac{\partial S}{S} = {\frac{ɛ_{1,2}}{S} \times \left( \frac{{dyR}_{1,2}}{dS} \right)^{- 1}}} & 7 \end{matrix}$

Where R_(1,2) is the ratiometric signal (equation 5), ε_(1,2) its experimental error, and δS is the resulting chemometric error in the concentration. We can then define a relative precision function

$\begin{matrix} {{P(S)} = {\frac{S}{\delta\; S} \times \frac{1}{P_{m\;{ax}}}}} & 8 \end{matrix}$

where P(S) is the relative precision at concentration S, which reaches a maximum value (i.e. lowest error), P_(max), at the K_(d).

For a given isothermal titration, values for ^(app)K_(d) and ^(true)K_(d) were obtained using a non-linear fitting algorithm in which these two parameters were simultaneously fit to the three experimental binding isotherms using equations 1 and 5, with the two monochromatic isotherms sharing the same ^(true)K_(d) value. Three separate pairs of ^(apo)β and ^(sat)β were fit in this procedure. Programs ‘Nanodrop3300’ and ‘TitrationMeltAnalysis’ were developed to analyze wavelength- or temperature-dependent ligand-binding datasets respectively. Analysis of temperature- and ligand-dependent fluorescent landscapes. To obtain the temperature dependence of the binding reaction, the K_(d) values of all the individually determined isotherms were fit the Gibbs-Hemholtz equation (Layton and Hellinga 2010 Biochemistry, 49, 10831-41):

$\begin{matrix} {{\Delta\;{G_{b}^{\bullet}(T)}} = {{\Delta^{ref}H_{b}^{\bullet}} + {\Delta\;{C_{p,b}\left( {T - T_{ref}} \right)}} - {T\left( {{\Delta^{ref}S_{b}^{\bullet}} + {\Delta\; C_{p,b}\ln\;\frac{T}{T_{ref}}}} \right)}}} & 9 \end{matrix}$

where ΔG._(b)(T) is the standard free energy of binding at 1 M ligand at temperature T,

$\begin{matrix} {{{\Delta G}_{b}^{\bullet}(T)} = {{- {RT}}\;{\ln\left( {1 + \frac{1}{K_{d}(T)}} \right)}}} & 10 \end{matrix}$

Δ^(ref) H._(b) and Δ^(ref) S._(b) the molar enthalpy and entropy of binding, respectively, at the reference temperature, T_(ref), and ΔC_(p,b) the heat capacity of the binding reaction. This data analysis was carried out using ‘TitrationMeltAnalysis’.

Analysis of emission spectra components. Wavelength-dependent, I(λ), emission intensities at were converted to wavenumber-dependent intensities (Valeur 2012 Principles and Applications. Weinheim: Wiley; Lakowicz 2006 Principles of fluorescence spectroscopy. Springer, N.Y.), I(v):

I(v)=λ² I(λ)   11

Singular value decomposition was used for model-free identification of regions in the emission spectra that vary with respect to glucose concentration (Henry 1992 Methods Enzymol, 210, 129-192). An A_(mn) data matrix was constructed by recording I(v) values of m frequencies in columns for n titration points in rows. This matrix was decomposed as

A_(min)=U_(mn)S_(nn)V_(nn) ^(T)   12

where U_(mn) records n spectral components at m frequencies ranked by the weight of their contribution to the reconstruction of the experimental data, V_(nn) records the contribution of the nth component to the n^(th) titration point, S_(nn) records the weight of the n^(th) component. Decomposition was carried using the in-house Nanodrop3300 program, written in Python. The linalg.svd method in the open-source Python scipy package (www.scipy.org, version 0.7.2) was used to solve the decomposition. The relative weight of the n^(th) component in U_(mn), f_(n), was calculated from S_(nn), by normalizing the values in S with its trace:

$\begin{matrix} {f_{n} = \frac{S_{nn}\left( {n,n} \right)}{{tr}\left( S_{nn} \right)}} & 13 \end{matrix}$

The fractional states of n individual electronic transitions in a spectrum were determined by fitting n Gaussians (Valeur 2012 Principles and Applications. Weinheim: Wiley.; Lakowicz 2006 Principles of fluorescence spectroscopy. Springer, N.Y.) to the emission intensities of the corrected spectra (equation 5) transformed into the frequency domain (equation 6):

$\begin{matrix} {{{{}_{}^{}{}_{}^{}}(v)} = {\sum\limits_{i = 1}^{i = n}{\frac{A_{i}}{\sqrt{2\pi}}e^{{- \frac{1}{2}}{(\frac{v - \mu_{i}}{\sigma})}^{2}}}}} & 14 \end{matrix}$

where μ_(i) is the wavenumber corresponding to the peak intensity of the i^(th) transition, A_(i) the area contributed to the total spectrum by this transition, and σ the spectral width of all transitions. The fraction, f_(i), of the i^(th) transition is given by:

$\begin{matrix} {f_{i} = \frac{A_{i}}{\sum\limits_{j = 1}^{j = n}A_{j}}} & 15 \end{matrix}$

Wavelength dependent residuals are given by:

Δ(v)=^(obs) I(v)−^(calc) I(v)   16

Fits were carried out by minimizing the least squares difference between observed and calculated spectra, using simplex and conjugate gradient methods implemented in Nanodrop3300 (scipy package methods optimize.fmin and optimize.leastsq, respectively). For titration series with N spectra, collected as a function of titrant concentration, global fits were used in which, as a first approximation, μi values were kept identical in the apo-protein and saturated glucose complex, and σ was universal for all transitions in all spectra. A_(i,k) values were allowed to vary in each k^(th) spectrum. The variation of the fraction for each transition, f_(i,k), was then fit to a binding isotherm (equation 1), constraining the fit ^(app)K_(d) value to be common to all transitions.

Structure determination by X-ray crystallography. Glucose-binding protein fluorescent conjugates were mixed with 2 mM D-glucose, and 1 mM CaCl₂. Sitting-drop vapor-diffusion Crystallization trials were carried out at 17° C. using sparse-matrix screening conditions. The ecGGBP183C⋅Acrylodan, ttGGBP182C⋅Acrylodan and ttGGBP.17C⋅Badan conjugates crystallized in 20% PEG 3350 and 0.2 M potassium thiocyanate as clusters of needles. Single crystals were isolated mechanically (Micro-Tools, Hampton Research), transferred stepwise into mother liquor containing 30% ethylene glycol, and flash-frozen in liquid nitrogen. Diffraction data was collected remotely at the Advanced Photon Source, SER-CAT beamline 22-ID; 0.5° oscillation angle frames were collected and processed using XDS program (Kabsch 2010 Acta Cryst., D66, 125-132). The data was phased by molecular replacement using PHASER (MCCoy 2007 J. Appl. Cryst., D66, 125-312) with a poly-alanine of the E. coli glucose-galactose-binding protein (2gbp (Vyas et al. 1988 Science, 242, 1290-5)) as the search model. Initial models were built after 10 cycles of rigid-body refinement in PHENIX, AutoBuild (Adams 2010 Acta Crystallogr D Biol Crystallogr, 66, 213-331). Multiple rounds of positional, individual B-factor and occupancy refinement and subsequent model building were performed in PHENIX and COOT, respectively. Solvent molecules were added both automatically as implemented in phenix.refine and by manual inspection. The structures were validated using PHENIX tools. The final refined models has crystallographic R_(factor) and R_(free) values that were within the range of average values refined at these resolutions(Kleywegt 1996 Structure, 4, 897-904).

EXAMPLE 14 FRS Uses

The glucose sensors can be incorporated into point-of-care clinical devices to measure glucose concentrations accurately, and rapidly at the patient bedside. In such a device, a small blood sample (<10 μL) is obtained by means of a finger stick using a lancet. This sample droplet is then placed on the aperture of a disposable cartridge containing desiccated, immobilized glucose sensors inside a small measurement chamber. The sample enters the chamber by virtue of passive capillary action, wetting the sensors upon contact. As soon as the sensors have been wetted, they bind glucose, and report on its concentration by virtue of the engineered fluorescent sensor mechanism. The cartridge is placed inside a small reader (handheld or on a desktop), and their fluorescence signal is measured by the (inexpensive) optoelectronic components of the reader. Excitation light is provided by a light-emitting diode (LED. In the case of Acrylodan or Badan, a commercially available 400 nm blue LED is used, and the emitted light is measured through two bandpass filters. Cartridges can contain multiple sensors, spanning the entire clinical range of possible glucose concentrations. Each sensor is immobilized at a particular, known location inside the cartridge, providing “spatial addressability”. The intensity at a particular wavelength is then recorded by imagining these sensors using an inexpensive camera, such as a Complementary metal-oxide semiconductor (CMOS) device commonly found in consumer electronics such as cell phones. Each pixel in the camera records the emitted light on a gray scale. Integration of that signal imaged through the two signals, is analyzed by an on-board computer to calculate the ratiometric signal for each immobilized sensor. Pre-recorded hyperbolic binding curves are then used to calculate the glucose concentration in the sample. Recording through multiple sensors, tuned for accurate detection at different glucose concentrations provides a high-accuracy reading. This process is completed in less than a minute.

Similar instrumentation can be used for any type of episodic measurements, for instance, using other bodily fluids, or samples obtained from animals, or non-biological samples such as foods and beverages.

The FRS glucose sensors also can be used to monitor glucose levels continuously. For instance, sensors can be immobilized at the tip of a thin optical fiber to construct a glucose-responsive optode. Such an optode can be introduced into the body subcutaneously, using a small needle. Excitation and emission light are passed to and from the immobilized sensor, respectively. The sensor is in continuous contact with the sample. Fluctuations in the glucose sample alter the dynamic equilibrium between the open and closed states of the glucose-binding protein, which is transduced into fluctuations of the fluorescent emission signal, by virtue of the sensing mechanism of the conjugated fluorophore. The emitted light intensities are read through filters by a reader connected to the optode. This reader continuously displays the change in signal, and the corresponding calculated glucose concentrations. Continuous glucose monitoring accomplished using a device containing the immobilized glucose biosensor(s), e.g., a fiber optic biosensor, introduced into the subject intradermally or subcutaneously (Judge et al., 2011, Diabetes Technology & Therapeutics 13 (3):309-317; Weidemaier et al., 2011, Biosensors and Bioelectronics 26:4117-4123; hereby incorporated by reference). For example, subcutaneously placed sensors can be used to monitor the glucose levels in a patient, guiding automated delivery of insulin in an artificial pancreas.

Similar instrumentation can be used to monitor glucose levels in a fermentor or bioreactor, coupled to automated injection of glucose for growth optimization of bacteria, fungi, and eukaryotic cells.

As was discussed above, the features that distinguish the described constructs, devices, and methods from earlier glucose assay systems include:

-   -   Self-calibration     -   Rapid response time     -   Simple sample-handling fluidic circuitry     -   No additional components/substrates (“reagentless”)     -   No incubation time to develop signal. Reading is         near-instantaneous and continuous     -   Stability (simplifies manufacturing, distribution, storage)     -   Small sample volume (<10 μL).     -   Capable of precise measurements over extended glucose         concentration range (from the hypoglycemic to the         hyperglycemic-hyperosmotic range)     -   Multiple sensors also provides redundancy, lowering error     -   Large scope of uses: episodic, continuous, ex vivo, in vivo,         optodes, implants.

Other Embodiments

While the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

The patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art. All United States patents and published or unpublished United States patent applications cited herein are incorporated by reference. All published foreign patents and patent applications cited herein are hereby incorporated by reference. Genbank and NCBI submissions indicated by accession number cited herein are hereby incorporated by reference. All other published references, documents, manuscripts and scientific literature cited herein are hereby incorporated by reference.

While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. 

1. A biosensor for a ligand, comprising a ligand-binding protein and a reporter group attached to said ligand-binding protein, wherein binding of said ligand to a ligand-binding domain of said ligand-binding protein causes a change in signaling by said reporter group, wherein said ligand comprises glucose or galactose, and wherein if said ligand-binding protein is an Escherichia coli (E. coli) glucose-galactose binding protein, then said ligand-binding protein comprises a mutation other than a mutation of amino acid Y10, D14, N15, F16, N91, K92, E93, S112, S115, E149, H152, D154, A155, R158, M182, W183, N211, D236, L255, N256, D257, P294, or V296, wherein each amino acid position is numbered as in (SEQ ID NO: 17).
 2. (canceled)
 3. (canceled)
 4. The biosensor of claim 1, wherein said ligand-binding protein comprises a mutation compared to a naturally occurring protein, and wherein at least one amino acid of the ligand-binding protein has been substituted with a cysteine.
 5. The biosensor of claim 1, wherein said ligand-binding protein comprises a mutation compared to a naturally occurring protein, and wherein said ligand-binding protein has no deletions or insertions compared to the naturally occurring protein.
 6. The biosensor of claim 1, wherein said ligand-binding protein comprises a mutation compared to a naturally occurring protein, and wherein said ligand-binding protein comprises (i) less than about 5, 4, 3, 2, or 1 inserted amino acids, and/or (ii) less than about 5, 4, 3, 2, or 1 deleted amino acids compared to the naturally occurring protein.
 7. (canceled)
 8. The biosensor of claim 1, wherein said ligand-binding protein comprises a mutant of a microbial glucose-galactose binding protein, and wherein said mutant comprises a mutation that alters the mutant's affinity and/or specificity for glucose and/or galactose compared to the microbial glucose-galactose binding protein.
 9. The biosensor of claim 1, wherein said ligand-binding protein is or is a mutant of: an Escherichia sp. GGBP; a Thermoanaerobacter sp. GGBP; a Clostridium sp. GGBP; a Salmonella sp. GGBP; a Caldicellulosiruptor sp. GGBP; a Paenibacillus sp. GGBP; a Butyrivibrio sp. GGBP; a Roseburia sp. GGBP; a Faecalibacterium sp. GGBP; an Erysipelothrix sp. GGBP; or an Eubacterium sp. GGBP.
 10. The biosensor of claim 1, wherein said ligand-binding protein is or is a mutant of: an Escherichia coli GGBP (ecGGBP; SEQ ID NO: 1 or 16), a Thermoanaerobacter thermosaccharolyticum GGBP (ttGGBP; SEQ ID NO: 2 or 18), a Salmonella typhimurium GGBP (stGGBP; SEQ ID NO: 3 or 19), a Caldicellulosiruptor hydrothermalis GGBP (chyGGBP; SEQ ID NO: 4 or 20), a Caldicellulosiruptor obsidiansis GGBP (cobGGBP; SEQ ID NO: 5 or 21), a Paenibacillus sp. GGBP (pspGGBP; SEQ ID NO: 6 or 22); a Clostridium saccharolyticum GGBP (csaGGBP; SEQ ID NO: 7 or 23); a Clostridium autoethanogenum GGBP (cauGGBP; SEQ ID NO: 12 or 28); a Clostridium ljungdahlii GGBP (clj GGBP; SEQ ID NO: 11 or 27); a Butyrivibrio proteoclasticus GGBP (bprGGBP; SEQ ID NO: 8 or 24); a Roseburia intestinalis GGBP (finGGBP_A; SEQ ID NO: 9 or 25 or rinGGBP_B; SEQ ID NO: 13 or 29); a Faecalibacterium prausnitzii GGBP (fprGGBP; SEQ ID NO: 10 or 26); a Erysipelothrix rhusiopathiae GGBP (erhGGBP; SEQ ID NO: 14 or 30); or a Eubacterium rectale GGBP (ereGGBP; SEQ ID NO: 15 or 31).
 11. The biosensor of claim 1, wherein said glucose-galactose binding protein comprises an amino acid sequence that is between 10% and 100% identical to the amino acid sequence of ecGGBP (SEQ ID NO: 1 or 16), ttGGBP (SEQ ID NO: 2 or 18), stGGBP (SEQ ID NO: 3 or 19), chyGGBP (SEQ ID NO: 4 or 20), pspGGBP (SEQ ID NO: 6 or 22); csaGGBP (SEQ ID NO: 7 or 23); bprGGBP (SEQ ID NO: 8 or 24); rinGGBP A (SEQ ID NO: 9 or 25); rinGGBP B (SEQ ID NO: 13 or 29); fprGGBP (SEQ ID NO: 10 or 26); cljGGBP (SEQ ID NO: 11 or 27); cauGGBP (SEQ ID NO: 12 or 28); erhGGBP (SEQ ID NO: 14 or 30); and/or ereGGBP (SEQ ID NO: 15 or 31).
 12. The biosensor of claim 1, wherein said ligand-binding protein comprises (a) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 10 of ecGGBP; (b) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 14 of ecGGBP; (c) a stretch of at least 5 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 91 of ecGGBP; (d) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 149 of ecGGBP; (e) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 150 of ecGGBP; (f) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 155 of ecGGBP; (g) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 160 of ecGGBP; (h) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 183 of ecGGBP; (i) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 210 of ecGGBP; (j) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 235 of ecGGBP; (k) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 240 of ecGGBP; (l) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 255 of ecGGBP; or (m) a stretch of at least 5 amino acids having at least about 50% identity to a stretch of consecutive amino acids including position 260 of ecGGBP, wherein each ecGGBP amino acid position is numbered as in SEQ ID NO:
 17. 13. (canceled)
 14. The biosensor of claim 1, wherein when said ligand-binding protein shares a primary complementary surface (PCS) with ecGGBP, wherein the PCS of ecGGBP comprises positions 14, 16, 91, 152, 154, 158, 183, 211, 236, and 256, wherein each position is counted as in SEQ ID NO: 17, and wherein when the amino acid sequence of said ligand-binding protein is aligned with ecGGBP (SEQ ID NO: 17), then said amino acid sequence comprises (i) D or N at the position that aligns with position 14 of ecGGBP; (ii) F, Y, or W at the position that aligns with position 16 of ecGGBP; (iii) N or D at the position that aligns with position 91 of ecGGBP; (iv) H, N, or Q at the position that aligns with position 152 of ecGGBP; (v) D or N at the position that aligns with position 154 of ecGGBP; (vi) R at the position that aligns with position 158 of ecGGBP; (vii) W, F, or Y at the position that aligns with position 183 of ecGGBP; (viii) N or D at the position that aligns with position 211 of ecGGBP; (ix) D or N at the position that aligns with position 236 of ecGGBP; and (x) N or D at the position that aligns with position 256 of ecGGBP.
 15. (canceled)
 16. (canceled)
 17. The biosensor of claim 1, wherein the C_(α) root-mean-square deviation (RMSD) between the backbone of the ligand-binding polypeptide and ecGGBP, ttGGBP, stGGBP, chyGGBP, cobGGBP, pspGGBP, csaGGBP, bprGGBP, rinGGBP_A, rinGGBP_B, fprGGBP, cljGGBP, cauGGBP, erhGGBP, ereGGBP, and/or chyGGBP is between about 0.1-3, 0.5-1, 0.5-1.5, or 0.5-2, or less than about 0.1 Å, 0.2 Å, 0.3 Å, 0.4 Å, 0.5 Å, 0.6 Å, 0.7 Å, 0.8 Å, 0.9 Å, 1.0 Å, 1.5 Å, 1.6 Å, 1.7 Å, 1.8 Å, 1.9 Å, 2.0 Å, 2.5 Å, or 3 Å.
 18. The biosensor of claim 1, wherein said ligand-binding protein is a mutant of ecGGBP comprising one or more of the following substitutions: Y10X, D14X, N15X, F16X, P70X, N91X, K92X, S112X, S115X, E149X, H152X, P153X, D154X, A155X, R158X, M182X, W183X, N211X, D212X, D236X, L238X, D257X, P294X, and V296X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in ecGGBP without including the signal peptide (SEQ ID NO: 17).
 19. (canceled)
 20. The biosensor of claim 1, wherein said reporter group is covalently attached to said ligand-binding protein.
 21. (canceled)
 22. (canceled)
 23. The biosensor of claim 1, wherein said reporter group is conjugated to a cysteine of the ligand-binding protein.
 24. (canceled)
 25. The biosensor of claim 1, wherein said reporter group comprises a fluorophore, and wherein said signal comprises a fluorescent signal.
 26. (canceled)
 27. (canceled)
 28. (canceled)
 29. The biosensor of claim 25, wherein an emission spectrum of said fluorophore exhibits hypsochromicity or bathochromicity upon ligand binding to the ligand-binding domain of said ligand-binding protein.
 30. (canceled)
 31. The biosensor of claim 25, wherein said fluorophore comprises 5-iodoacetamidofluorescein (5IAF) or 6-iodoacetamidofluorescein (6IAF), rhodamine, Oregon Green, eosin, Texas Red, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, Badan, Acrylodan, IAEDANS, comprising 3-cyano-7-hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy-4-methylcoumarin, or 7-amino-4-methylcoumarin, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, DRAQS, DRAQ7, or CyTRAK Orange, cascade blue, Nile red, Nile blue, cresyl violet, oxazine 170, proflavin, acridine orange, acridine yellow, auramine, crystal violet, malachite green, porphin, phthalocyanine, bilirubin, pyrene, N,N′-dimethyl-N-(iodoacetyl)-N′-(7-nitrobenz-2-ox-a-1,3-diazol-4-yl)ethylenediamide (NBD), N-((2-(iodoacetoxy)ethyl)-N-methy-1)amino-7-nitrobenz-2-oxa-1,3-diazole (NBDE), Acrylodan, JPW4039, JPW4042, JPW4045, Oregon Green, Pacific Blue, N,N′-Dimethyl-N-(Iodoacetyl)-N′-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Ethylenediamine (IANBD), 7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin (CPM), BODIPY 499, BODIPY 507, Alexa488, Alexa532, Alexa546, Cy5, or 1-(2-maleimidylethyl)-4-(5-(4-methoxyphenyl)oxazol-2-yl)pyridinium methanesulfonate (PyMPO maleimide) (PyMPO).
 32. The biosensor of claim 25, comprising Acrylodan (6-acryloy 1-2-dimethylaminonaphthalene) or Badan (6-bromo-acetyl-2-dimethylamino-naphthalene) or a derivative thereof.
 33. The biosensor of claim 32, wherein said derivative comprises a replacement of the two-ring naphthalene of Acrylodan or Badan with a three-ring anthracene, a fluorene, or a styrene.
 34. (canceled)
 35. (canceled)
 36. A method of detecting the presence of a ligand in a sample, the method comprising: (a) contacting the biosensor of claim 1 with the sample; (b) measuring a signal from the biosensor; and (c) comparing the signal to a ligand-free control, wherein a difference in signal indicates the presence of ligand in the sample, and wherein the ligand comprises glucose, galactose, or combination thereof. 37.-51. (canceled)
 52. A method for monitoring the level of a ligand in a subject, comprising (a) administering a biosensor according to claim 1 or a device comprising a biosensor according to claim 1 to said subject, wherein after administration the biosensor is in contact with a bodily fluid or surface of said subject, and (b) detecting (i) a signal produced by a reporter group of said biosensor continuously or repeatedly at intervals less than about 30 minutes apart, and/or (ii) whether a signal is produced by a reporter group of said biosensor continuously or repeatedly at intervals less than about 30 minutes apart. 53.-82. (canceled) 